Is CD70 p.Arg192Ser (c.574C>A) pathogenic?

CD70 p.Arg192Ser (c.574C>A) is classified Uncertain significance in CD70 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.3243); Very rare (popmax 0.00187%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CD70 p.Arg192Ser (c.574C>A)?

CD70 p.Arg192Ser (c.574C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CD70 p.Arg192Ser (c.574C>A) in the general population?

CD70 p.Arg192Ser (c.574C>A) is very rare (popmax 0.00187%, nfe) (gnomAD).

What do computational predictors say about CD70 p.Arg192Ser (c.574C>A)?

AlphaMissense predicts likely benign (score 0.3243) — an in-silico prediction, not a clinical call.

CD70 p.Arg192Ser

c.574C>A · rs182050995 · VCV2602445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3243 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3243	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -3.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.49	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.69	GERP 0.44
Regional constraint	o/e 0.91	unconstrained · MANE · 4,979 bp · p 0.14 · regional, not allelic
Overall
CADD	10.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00187% European (non-Finnish) · 22/1,174,772 alleles

Filtering AF 0.00123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00199% 32/1,607,796 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0271%	3,689
Remaining individualsnot grpmax-eligible	0.00321%	31,155
European (non-Finnish)grpmax	0.00187%	53,399

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CD70
Protein: p.Arg192Ser
Coding: c.574C>A
MANE Select: NM_001252
dbSNP: rs182050995
Type: single nucleotide variant
Location: chr19:6586028 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 192: a UniProt-annotated variant site (in lpfs3; loss of protein expression); a UniProt-annotated variant site (in lpfs3; no effect on protein expression; loss of interaction with cd27); a β-strand

Full CD70 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD70 p.Leu23Phe Uncertain significance ★★ ⚠ same condition
CD70 p.Ser9Leu Uncertain significance ★★ ⚠ same condition
CD70 p.Thr118Met Uncertain significance ★★ ⚠ same condition
CD70 p.Thr119Met Uncertain significance ★★ ⚠ same condition
CD70 p.Val130Met Uncertain significance ★★ ⚠ same condition
CD70 p.Ala129Gly Uncertain significance ★ ⚠ same condition
CD70 p.Ala136Pro Uncertain significance ★ ⚠ same condition
CD70 p.Ala136Thr Uncertain significance ★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cd70-p-arg192ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown