Is CD38 p.Pro281Ser (c.841C>T) pathogenic?

CD38 p.Pro281Ser (c.841C>T) is classified Uncertain significance in CD38 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: likely benign (0.1663); Very rare (popmax 0.00535%, afr).

How common is CD38 p.Pro281Ser (c.841C>T) in the general population?

CD38 p.Pro281Ser (c.841C>T) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about CD38 p.Pro281Ser (c.841C>T)?

AlphaMissense predicts likely benign (score 0.1663) — an in-silico prediction, not a clinical call.

CD38 p.Pro281Ser

c.841C>T · VCV3829564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1663	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -7.83	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 -0.033	GERP -0.2, phastCons 0.025
Regional constraint	o/e 1.02	unconstrained · MANE · 70 kb · p 0.67 · regional, not allelic
Overall
CADD	8.602	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 0.00535% African / African-American · 4/74,832 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.00304% 49/1,610,982 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,708
European (non-Finnish)	0.00365%	27,380
South Asian	0.0022%	45,494

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.Pro281Ser
Coding: c.841C>T
MANE Select: NM_001775
Type: single nucleotide variant
Location: chr4:15848540 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 56 PDB
Residue 281: 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-pro281ser (accessed [today's date]).

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