Is CD70 p.Thr119Met (c.356C>T) pathogenic?

CD70 p.Thr119Met (c.356C>T) is classified Uncertain significance in CD70 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-08). AlphaMissense: likely benign (0.1118); Ultra-rare (popmax 0.0213%, afr); Associated with Inborn genetic diseases.

What condition is associated with CD70 p.Thr119Met (c.356C>T)?

CD70 p.Thr119Met (c.356C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CD70 p.Thr119Met (c.356C>T) in the general population?

CD70 p.Thr119Met (c.356C>T) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

What do computational predictors say about CD70 p.Thr119Met (c.356C>T)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

CD70 p.Thr119Met

c.356C>T · VCV3380561

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.001	GERP -2.4
Regional constraint	o/e 0.91	unconstrained · MANE · 4,979 bp · p 0.14 · regional, not allelic
Overall
CADD	1.587	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 0.0213% African / African-American · 16/75,024 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00372% 60/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,689
European (non-Finnish)	0.00347%	28,780
East Asian	0.00223%	44,872
Admixed American	0.00167%	60,020
South Asian	0.0011%	91,082

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.Thr119Met
Coding: c.356C>T
MANE Select: NM_001252
Type: single nucleotide variant
Location: chr19:6586246 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 119: the thd domain; an α-helix; a disulfide bond

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.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
CD70 p.Arg192Ser 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-thr119met (accessed [today's date]).

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