Is CD38 p.Asp179Gly (c.536A>G) pathogenic?

CD38 p.Asp179Gly (c.536A>G) is classified Uncertain significance in CD38 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: ambiguous (0.3828); Very rare (popmax 0.00814%, nfe).

How common is CD38 p.Asp179Gly (c.536A>G) in the general population?

CD38 p.Asp179Gly (c.536A>G) is very rare (popmax 0.00814%, nfe) (gnomAD).

What do computational predictors say about CD38 p.Asp179Gly (c.536A>G)?

AlphaMissense predicts ambiguous (score 0.3828) — an in-silico prediction, not a clinical call.

CD38 p.Asp179Gly

c.536A>G · rs201816957 · VCV2522216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3828 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00814%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3828	ambiguous
REVEL	0.172	moderately benign-leaning
SaProt	LLR -6.01	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.30	donor loss, 49 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 70 kb · p 0.67 · regional, not allelic
Overall
CADD	21.5	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 0.00814% European (non-Finnish) · 96/1,178,976 alleles

Filtering AF 0.00681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00614% 99/1,612,952 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00814%	12,281
Remaining individualsnot grpmax-eligible	0.0048%	20,819

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: CD38
Protein: p.Asp179Gly
Coding: c.536A>G
MANE Select: NM_001775
dbSNP: rs201816957
Type: single nucleotide variant
Location: chr4:15834253 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 56 PDB
Residue 179: a disulfide bond; a turn

Full CD38 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD38 p.Tyr70= Benign ★★ same type
CD38 c.752+2T>C Uncertain significance ★ same type
CD38 p.Ala154Val Uncertain significance ★ ⚠ same type
CD38 p.Arg17Trp Uncertain significance ★ ⚠ same type
CD38 p.Arg194Cys Uncertain significance ★ ⚠ same type
CD38 p.Arg195Gly Uncertain significance ★ ⚠ same type
CD38 p.Asn169Ser Uncertain significance ★ ⚠ same type
CD38 p.Asn209His Uncertain significance ★ ⚠ 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/cd38-p-asp179gly (accessed [today's date]).

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