Is ENTPD4 p.Ala267= (c.801G>A) pathogenic?

ENTPD4 p.Ala267= (c.801G>A) is classified Likely benign in ENTPD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Rare (popmax 0.437%, nfe).

How common is ENTPD4 p.Ala267= (c.801G>A) in the general population?

ENTPD4 p.Ala267= (c.801G>A) is rare (popmax 0.437%, nfe) (gnomAD).

ENTPD4 p.Ala267=

c.801G>A · rs113598172 · VCV2658481

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.437%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -3.8
Overall
CADD	3.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.437% European (non-Finnish) · 5,155/1,180,034 alleles

Filtering AF 0.427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.423%

Overall 0.38% 6,137/1,614,190 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.734%	136
European (non-Finnish)grpmax	0.437%	229
Ashkenazi Jewishnot grpmax-eligible	0.436%	229
Remaining individualsnot grpmax-eligible	0.339%	295
Admixed American	0.16%	625
African / African-American	0.0533%	1,876
Middle Eastern	0.0495%	2,021
South Asian	0.0307%	3,253
East Asian	0.00891%	11,222

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala267=
Coding: c.801G>A
MANE Select: NM_004901
dbSNP: rs113598172
Type: single nucleotide variant
Location: chr8:23441650 (GRCh38)
Gene constraint: LOEUF 0.905 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.51 · 1 PDB

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

Similar variants

ENTPD4 p.Ala267Val Uncertain significance ★ ⚠ same residue
ENTPD4 p.Ala167Glu Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala214Thr Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala246Gly 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-ala267 (accessed [today's date]).

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