Is ENTREP1 p.Arg314Gln (c.941G>A) pathogenic?

ENTREP1 p.Arg314Gln (c.941G>A) is classified Uncertain significance in ENTREP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.093); Ultra-rare (popmax 0.01%, amr).

How common is ENTREP1 p.Arg314Gln (c.941G>A) in the general population?

ENTREP1 p.Arg314Gln (c.941G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about ENTREP1 p.Arg314Gln (c.941G>A)?

AlphaMissense predicts likely benign (score 0.093) — an in-silico prediction, not a clinical call.

ENTREP1 p.Arg314Gln

c.941G>A · rs141626167 · VCV3089180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.093 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.093	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -7.26	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 9.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 58 kb · p 0.22 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R161Q vs ClinVar R314Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,904 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00186% 30/1,612,766 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,984
African / African-American	0.00935%	10,698
Remaining individualsnot grpmax-eligible	0.0032%	31,210
European (non-Finnish)	0.00127%	78,639

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: ENTREP1
Protein: p.Arg314Gln
Coding: c.941G>A
MANE Select: NM_001347995
dbSNP: rs141626167
Type: single nucleotide variant
Location: chr9:69377732 (GRCh38)
Structure: AlphaFold pLDDT 60.47
Residue 314: the 'mediates interaction with epn1' region

Full ENTREP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTREP1 p.Arg314Trp Uncertain significance ★ ⚠ same residue
ENTREP1 p.Ala374Ser Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala418Asp Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala440Ser Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala440Thr Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala448Ser Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala492Val Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala574Pro 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/entrep1-p-arg314gln (accessed [today's date]).

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