Is EHBP1 p.Pro254Ser (c.760C>T) pathogenic?

EHBP1 p.Pro254Ser (c.760C>T) is classified Uncertain significance in EHBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). AlphaMissense: likely benign (0.0803); Very rare (popmax 0.0017%, amr).

How common is EHBP1 p.Pro254Ser (c.760C>T) in the general population?

EHBP1 p.Pro254Ser (c.760C>T) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about EHBP1 p.Pro254Ser (c.760C>T)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

EHBP1 p.Pro254Ser

c.760C>T · rs2470323142 · VCV2526116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.02	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 1.4	GERP 0.44, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 112 kb · p 0.83 · regional, not allelic
Overall
CADD	15.91	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 P289S vs ClinVar P254S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% Admixed American · 1/58,936 alleles

Filtering AF 0.000765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000607%

Overall 0.0011% 16/1,455,164 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,936
European (non-Finnish)	0.00127%	78,479

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: EHBP1
Protein: p.Pro254Ser
Coding: c.760C>T
MANE Select: NM_001142616
dbSNP: rs2470323142
Type: single nucleotide variant
Location: chr2:62864733 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.13 · 4 PDB

Full EHBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EHBP1 c.1185+30064G>A Uncertain significance ★★ same type
EHBP1 c.2609-2750G>A Uncertain significance ★ ⚠ same type
EHBP1 c.2609-2755A>G Uncertain significance ★ ⚠ same type
EHBP1 c.2609-2762G>T Uncertain significance ★ ⚠ same type
EHBP1 c.635-674G>A Uncertain significance ★ ⚠ same type
EHBP1 c.635-679A>G Uncertain significance ★ ⚠ same type
EHBP1 c.635-688G>A Uncertain significance ★ ⚠ same type
EHBP1 c.635-718A>T 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/ehbp1-p-pro254ser (accessed [today's date]).

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