Is EHF p.Arg95Trp (c.283C>T) pathogenic?

EHF p.Arg95Trp (c.283C>T) is classified Uncertain significance in EHF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: likely benign (0.1472); Ultra-rare (popmax 0.0164%, mid).

How common is EHF p.Arg95Trp (c.283C>T) in the general population?

EHF p.Arg95Trp (c.283C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about EHF p.Arg95Trp (c.283C>T)?

AlphaMissense predicts likely benign (score 0.1472) — an in-silico prediction, not a clinical call.

EHF p.Arg95Trp

c.283C>T · rs369404357 · VCV2370588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1472 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1472	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -8.81	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 0.61	GERP -1.2, phastCons 0.048
Regional constraint	o/e 0.86	unconstrained · MANE · 14 kb · p 0.029 · regional, not allelic
Overall
CADD	21.2	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00341% 55/1,613,582 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
South Asian	0.00549%	18,206
European (non-Finnish)	0.00381%	26,220
Remaining individualsnot grpmax-eligible	0.0032%	31,239
Admixed American	0.00167%	59,984
Finnishnot grpmax-eligible	0.00157%	63,872

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: EHF
Protein: p.Arg95Trp
Coding: c.283C>T
MANE Select: NM_012153
dbSNP: rs369404357
Type: single nucleotide variant
Location: chr11:34646624 (GRCh38)
Gene constraint: LOEUF 0.483 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 69.12 · 1 PDB
Residue 95: the pnt domain

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

Similar variants

EHF p.Arg95Gln Uncertain significance ★ ⚠ same residue
EHF p.Val128= Benign ★★ same type
EHF c.-3-10022G>T Uncertain significance ★ same type
EHF c.-3-9995T>C Uncertain significance ★ same type
EHF p.Arg168Gln Uncertain significance ★ ⚠ same type
EHF p.Arg168Gly Uncertain significance ★ same type
EHF p.Arg214His Uncertain significance ★ ⚠ same type
EHF p.Arg232Gln 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/ehf-p-arg95trp (accessed [today's date]).

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