Is CD38 p.Cys287Phe (c.860G>T) pathogenic?

CD38 p.Cys287Phe (c.860G>T) is classified Uncertain significance in CD38 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: ambiguous (0.4171); Very rare (popmax 0.000339%, nfe).

How common is CD38 p.Cys287Phe (c.860G>T) in the general population?

CD38 p.Cys287Phe (c.860G>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CD38 p.Cys287Phe (c.860G>T)?

AlphaMissense predicts ambiguous (score 0.4171) — an in-silico prediction, not a clinical call.

CD38 p.Cys287Phe

c.860G>T · VCV4222901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4171 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4171	ambiguous
REVEL	0.294	indeterminate
SaProt	LLR -12.67	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP -0.29, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 70 kb · p 0.67 · regional, not allelic
Overall
CADD	22.1	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 0.000339% European (non-Finnish) · 4/1,179,810 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,742 alleles · very rare

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.Cys287Phe
Coding: c.860G>T
MANE Select: NM_001775
Type: single nucleotide variant
Location: chr4:15848559 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 56 PDB
Residue 287: a disulfide bond; an α-helix

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-cys287phe (accessed [today's date]).

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