Is ENTPD2 p.Phe348Val (c.1042T>G) pathogenic?

ENTPD2 p.Phe348Val (c.1042T>G) is classified Uncertain significance in ENTPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely pathogenic (0.6269); Rare (popmax 0.136%, eas).

How common is ENTPD2 p.Phe348Val (c.1042T>G) in the general population?

ENTPD2 p.Phe348Val (c.1042T>G) is rare (popmax 0.136%, eas) (gnomAD).

What do computational predictors say about ENTPD2 p.Phe348Val (c.1042T>G)?

AlphaMissense predicts likely pathogenic (score 0.6269) — an in-silico prediction, not a clinical call.

ENTPD2 p.Phe348Val

c.1042T>G · rs552264498 · VCV3089056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6269 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.136%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6269	likely pathogenic
REVEL	0.49	indeterminate
SaProt	LLR -10.81	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,337 bp · p 0.028 · regional, not allelic
Overall
CADD	28.5	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 0.136% East Asian · 61/44,828 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0988%

Overall 0.00434% 70/1,611,976 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.136%	735
Middle Eastern	0.0166%	6,036
Remaining individualsnot grpmax-eligible	0.0032%	31,218
African / African-American	0.00267%	37,453
European (non-Finnish)	0.000339%	294,877

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: ENTPD2
Protein: p.Phe348Val
Coding: c.1042T>G
MANE Select: NM_203468
dbSNP: rs552264498
Type: single nucleotide variant
Location: chr9:137049977 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.02

Full ENTPD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTPD2 p.Phe348Ser Uncertain significance ★ ⚠ same residue
ENTPD2 p.Arg193Gln Benign ★★ same type
ENTPD2 p.Val343= Benign ★★ same type
ENTPD2 p.Ala113Thr Uncertain significance ★ ⚠ same type
ENTPD2 p.Ala113Val Uncertain significance ★ ⚠ same type
ENTPD2 p.Ala16Gly Uncertain significance ★ ⚠ same type
ENTPD2 p.Ala17Thr Uncertain significance ★ ⚠ same type
ENTPD2 p.Ala199Ser 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/entpd2-p-phe348val (accessed [today's date]).

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