Is CD70 p.Ala129Gly (c.386C>G) pathogenic?

CD70 p.Ala129Gly (c.386C>G) is classified Uncertain significance in CD70 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: ambiguous (0.3472); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with CD70 p.Ala129Gly (c.386C>G)?

CD70 p.Ala129Gly (c.386C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CD70 p.Ala129Gly (c.386C>G) in the general population?

CD70 p.Ala129Gly (c.386C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CD70 p.Ala129Gly (c.386C>G)?

AlphaMissense predicts ambiguous (score 0.3472) — an in-silico prediction, not a clinical call.

CD70 p.Ala129Gly

c.386C>G · VCV4223011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3472 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3472	ambiguous
REVEL	0.278	benign-leaning
SaProt	LLR -7.64	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 0.78	GERP -2.8
Regional constraint	o/e 0.91	unconstrained · MANE · 4,979 bp · p 0.14 · regional, not allelic
Overall
CADD	7.689	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 0.00133% African / African-American · 1/74,934 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,613,962 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,934
European (non-Finnish)	0.000847%	117,999

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.Ala129Gly
Coding: c.386C>G
MANE Select: NM_001252
Type: single nucleotide variant
Location: chr19:6586216 (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

Disease context

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

Similar variants

CD70 p.Ala129Ser Likely benign ★ 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.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-ala129gly (accessed [today's date]).

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