Is CD70 p.Ala129Ser (c.385G>T) pathogenic?

CD70 p.Ala129Ser (c.385G>T) is classified Likely benign in CD70 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). AlphaMissense: likely benign (0.1013); Ultra-rare (popmax 0.0107%, afr).

How common is CD70 p.Ala129Ser (c.385G>T) in the general population?

CD70 p.Ala129Ser (c.385G>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about CD70 p.Ala129Ser (c.385G>T)?

AlphaMissense predicts likely benign (score 0.1013) — an in-silico prediction, not a clinical call.

CD70 p.Ala129Ser

c.385G>T · VCV4940151

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1013 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1013	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -4.30	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 -3.1	GERP -2.8
Regional constraint	o/e 0.91	unconstrained · MANE · 4,979 bp · p 0.14 · regional, not allelic
Overall
CADD	0.025	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 0.0107% African / African-American · 8/74,910 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.0031% 50/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,364
European (non-Finnish)	0.00339%	29,501
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Finnishnot grpmax-eligible	0.00156%	64,006

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.Ala129Ser
Coding: c.385G>T
MANE Select: NM_001252
Type: single nucleotide variant
Location: chr19:6586217 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.52 · 1 PDB
Residue 129: the thd domain; a β-strand; a disulfide bond

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

Similar variants

CD70 p.Ala129Gly Uncertain significance ★ ⚠ same residue
CD70 p.Leu23Phe Uncertain significance ★★ ⚠ same type
CD70 p.Ser146Ile Uncertain significance ★★ same type
CD70 p.Ser9Leu Uncertain significance ★★ ⚠ same type
CD70 p.Thr118Met Uncertain significance ★★ ⚠ same type
CD70 p.Thr119Met Uncertain significance ★★ ⚠ same type
CD70 p.Val130Met Uncertain significance ★★ ⚠ same type
CD70 p.Cys115= Benign ★★ same type

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-ala129ser (accessed [today's date]).

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