Is ENTREP1 p.Pro434His (c.1301C>A) pathogenic?

ENTREP1 p.Pro434His (c.1301C>A) is classified Likely benign in ENTREP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-23). AlphaMissense: likely benign (0.0489); Absent from gnomAD v4.1.

How common is ENTREP1 p.Pro434His (c.1301C>A) in the general population?

ENTREP1 p.Pro434His (c.1301C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENTREP1 p.Pro434His (c.1301C>A)?

AlphaMissense predicts likely benign (score 0.0489) — an in-silico prediction, not a clinical call.

ENTREP1 p.Pro434His

c.1301C>A · rs2133738248 · VCV2528686

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0489 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,652)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0489	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -7.11	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 3.1	GERP -0.63, phastCons 0.88
Regional constraint	o/e 0.98	unconstrained · MANE · 7,796 bp · p 0.71 · regional, not allelic
Overall
CADD	15.39	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P281H vs ClinVar P434H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,606,652). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ENTREP1
Protein: p.Pro434His
Coding: c.1301C>A
MANE Select: NM_001347995
dbSNP: rs2133738248
Type: single nucleotide variant
Location: chr9:69385933 (GRCh38)
Structure: AlphaFold pLDDT 60.47
Residue 434: the 'mediates interaction with epn1' region

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

Similar variants

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
ENTREP1 p.Ala588Val Conflicting classifications of pathogenicity ★ ⚠ 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-pro434his (accessed [today's date]).

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