Is ENTPD3 p.Ala140Val (c.419C>T) pathogenic?

ENTPD3 p.Ala140Val (c.419C>T) is classified Uncertain significance in ENTPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely pathogenic (0.8758); Very rare (popmax 0.00222%, sas).

How common is ENTPD3 p.Ala140Val (c.419C>T) in the general population?

ENTPD3 p.Ala140Val (c.419C>T) is very rare (popmax 0.00222%, sas) (gnomAD).

What do computational predictors say about ENTPD3 p.Ala140Val (c.419C>T)?

AlphaMissense predicts likely pathogenic (score 0.8758) — an in-silico prediction, not a clinical call.

ENTPD3 p.Ala140Val

c.419C>T · rs1955642686 · VCV3089074

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8758 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8758	likely pathogenic · top 8% in ENTPD3
REVEL	0.503	indeterminate
SaProt	LLR -12.18	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 39 kb · p 0.058 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00222% South Asian · 2/90,146 alleles

Filtering AF 0.000368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000137% 2/1,458,630 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: ENTPD3
Protein: p.Ala140Val
Coding: c.419C>T
MANE Select: NM_001248
dbSNP: rs1955642686
Type: single nucleotide variant
Location: chr3:40411944 (GRCh38)
Gene constraint: LOEUF 1.454 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.79

Full ENTPD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTPD3 p.Ala17Ser Uncertain significance ★ ⚠ same type
ENTPD3 p.Ala223Val Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg143His Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg292Gln Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg292Trp Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg419Cys Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg419His Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg479His 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/entpd3-p-ala140val (accessed [today's date]).

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