Is ENTPD5 p.Ser373Arg (c.1119T>A) pathogenic?

ENTPD5 p.Ser373Arg (c.1119T>A) is classified Uncertain significance in ENTPD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely pathogenic (0.7365); Very rare (popmax 0.004%, afr).

How common is ENTPD5 p.Ser373Arg (c.1119T>A) in the general population?

ENTPD5 p.Ser373Arg (c.1119T>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ENTPD5 p.Ser373Arg (c.1119T>A)?

AlphaMissense predicts likely pathogenic (score 0.7365) — an in-silico prediction, not a clinical call.

ENTPD5 p.Ser373Arg

c.1119T>A · VCV3845048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7365 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7365	likely pathogenic
REVEL	0.239	benign-leaning
SaProt	LLR -8.90	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	GERP -0.81, phastCons 0.97
Regional constraint	o/e 0.95	unconstrained · MANE · 21 kb · p 0.22 · regional, not allelic
Overall
CADD	22.8	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 0.004% African / African-American · 3/74,918 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00197% 3/152,210 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: ENTPD5
Protein: p.Ser373Arg
Coding: c.1119T>A
MANE Select: NM_001249
Type: single nucleotide variant
Location: chr14:73970091 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.55
Residue 373: a disulfide bond

Full ENTPD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COQ6 p.Glu413Asp Uncertain significance ★★ ⚠ same type
COQ6 p.His419Pro Uncertain significance ★★ ⚠ same type
COQ6 p.Val165Ile Uncertain significance ★★ ⚠ same type
COQ6 c.*146G>C Benign ★★ same type
COQ6 p.Asn245= Likely benign ★★ same type
COQ6 p.Leu444Ile Uncertain significance ★ ⚠ same type
COQ6 p.Ser437Thr Uncertain significance ★ ⚠ same type
ENTPD5 p.Ala257Thr 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/entpd5-p-ser373arg (accessed [today's date]).

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