Is CD70 p.Arg72Lys (c.215G>A) pathogenic?

CD70 p.Arg72Lys (c.215G>A) is classified Uncertain significance in CD70 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: ambiguous (0.3791); Ultra-rare (popmax 0.0198%, sas); Associated with Inborn genetic diseases.

What condition is associated with CD70 p.Arg72Lys (c.215G>A)?

CD70 p.Arg72Lys (c.215G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CD70 p.Arg72Lys (c.215G>A) in the general population?

CD70 p.Arg72Lys (c.215G>A) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

What do computational predictors say about CD70 p.Arg72Lys (c.215G>A)?

AlphaMissense predicts ambiguous (score 0.3791) — an in-silico prediction, not a clinical call.

CD70 p.Arg72Lys

c.215G>A · rs774636584 · VCV2537702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3791 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3791	ambiguous
REVEL	0.155	moderately benign-leaning
SaProt	LLR -9.59	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP 0.38
Regional constraint	o/e 0.91	unconstrained · MANE · 4,979 bp · p 0.14 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% South Asian · 18/90,938 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.0013% 21/1,610,202 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,052
Remaining individualsnot grpmax-eligible	0.00482%	20,754

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.Arg72Lys
Coding: c.215G>A
MANE Select: NM_001252
dbSNP: rs774636584
Type: single nucleotide variant
Location: chr19:6586387 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 72: a β-strand; the thd domain

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.Arg72Thr Uncertain significance ★ ⚠ same residue
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

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-arg72lys (accessed [today's date]).

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