Is ENTPD4 p.Val102Ile (c.304G>A) pathogenic?

ENTPD4 p.Val102Ile (c.304G>A) is classified Likely benign in ENTPD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely benign (0.0624); Very rare (popmax 8.47e-05%, nfe).

How common is ENTPD4 p.Val102Ile (c.304G>A) in the general population?

ENTPD4 p.Val102Ile (c.304G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ENTPD4 p.Val102Ile (c.304G>A)?

AlphaMissense predicts likely benign (score 0.0624) — an in-silico prediction, not a clinical call.

ENTPD4 p.Val102Ile

c.304G>A · rs2486755644 · VCV3089084

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0624 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0624	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -5.94	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 -0.086	GERP -4.1, phastCons 0.001
Regional constraint	o/e 1.00	unconstrained · MANE · 17 kb · p 0.91 · regional, not allelic
Overall
CADD	6.522	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 8.47e-05% European (non-Finnish) · 1/1,179,998 alleles

Overall 6.84e-05% 1/1,461,838 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: ENTPD4
Protein: p.Val102Ile
Coding: c.304G>A
MANE Select: NM_004901
dbSNP: rs2486755644
Type: single nucleotide variant
Location: chr8:23447788 (GRCh38)
Gene constraint: LOEUF 0.905 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.51 · 1 PDB
Residue 102: a β-strand

Full ENTPD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTPD4 p.Ala167Glu Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala214Thr Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala246Gly Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala267Val Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala280Val Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala462Glu Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala478Thr Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala547Val 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/entpd4-p-val102ile (accessed [today's date]).

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