Is EHF p.Lys272Arg (c.815A>G) pathogenic?

EHF p.Lys272Arg (c.815A>G) is classified Uncertain significance in EHF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: ambiguous (0.3987); Ultra-rare (popmax 0.0659%, mid).

How common is EHF p.Lys272Arg (c.815A>G) in the general population?

EHF p.Lys272Arg (c.815A>G) is ultra-rare (popmax 0.0659%, mid) (gnomAD).

What do computational predictors say about EHF p.Lys272Arg (c.815A>G)?

AlphaMissense predicts ambiguous (score 0.3987) — an in-silico prediction, not a clinical call.

EHF p.Lys272Arg

c.815A>G · rs1281720890 · VCV2407578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3987 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0659%, mid)

Computational evidence

Protein change
AlphaMissense	0.3987	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -9.46	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 93 bp · p 0.14 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0659% Middle Eastern · 4/6,072 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00112% 18/1,611,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0659%	1,518
African / African-American	0.00535%	18,683
East Asian	0.00223%	44,842
Admixed American	0.00168%	59,600
Remaining individualsnot grpmax-eligible	0.0016%	62,388
European (non-Finnish)	0.000594%	168,473

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.Lys272Arg
Coding: c.815A>G
MANE Select: NM_012153
dbSNP: rs1281720890
Type: single nucleotide variant
Location: chr11:34658843 (GRCh38)
Gene constraint: LOEUF 0.483 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 69.12 · 1 PDB
Residue 272: a DNA-binding region

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

Similar variants

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
EHF p.Arg293Gln 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-lys272arg (accessed [today's date]).

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