Is CD38 p.Pro60Ser (c.178C>T) pathogenic?

CD38 p.Pro60Ser (c.178C>T) is classified Uncertain significance in CD38 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.1215); Ultra-rare (popmax 0.0736%, sas).

How common is CD38 p.Pro60Ser (c.178C>T) in the general population?

CD38 p.Pro60Ser (c.178C>T) is ultra-rare (popmax 0.0736%, sas) (gnomAD).

What do computational predictors say about CD38 p.Pro60Ser (c.178C>T)?

AlphaMissense predicts likely benign (score 0.1215) — an in-silico prediction, not a clinical call.

CD38 p.Pro60Ser

c.178C>T · rs550670064 · VCV3140577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1215 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0736%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1215	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -6.32	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 -3.8	GERP -2
Regional constraint	o/e 1.02	unconstrained · MANE · 70 kb · p 0.67 · regional, not allelic
Overall
CADD	0.066	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 0.0736% South Asian · 67/91,070 alleles

Filtering AF 0.0593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00626% 101/1,613,766 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0736%	1,359
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	0.00186%	53,636
African / African-American	0.00133%	75,040

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.Pro60Ser
Coding: c.178C>T
MANE Select: NM_001775
dbSNP: rs550670064
Type: single nucleotide variant
Location: chr4:15778592 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 56 PDB
Residue 60: 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-pro60ser (accessed [today's date]).

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