Is EHF p.Val128= (c.384C>T) pathogenic?

EHF p.Val128= (c.384C>T) is classified Benign in EHF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-24). Low-frequency (popmax 2.24%, afr).

How common is EHF p.Val128= (c.384C>T) in the general population?

EHF p.Val128= (c.384C>T) is low-frequency (popmax 2.24%, afr) (gnomAD).

EHF p.Val128=

c.384C>T · rs12721519 · VCV789794

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.24%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.1, phastCons 1
Overall
CADD	10.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.24% African / African-American · 1,683/75,044 alleles

Filtering AF 2.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.12%

Overall 0.117% 1,888/1,614,008 alleles · low-frequency exomes 929/1,461,668 · genomes 959/152,340 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.24%	45
Remaining individualsnot grpmax-eligible	0.16%	625
Admixed American	0.13%	770
Middle Eastern	0.0664%	1,506
South Asian	0.00549%	18,211
European (non-Finnish)	0.00153%	65,552

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.Val128=
Coding: c.384C>T
MANE Select: NM_012153
dbSNP: rs12721519
Type: single nucleotide variant
Location: chr11:34649059 (GRCh38)
Gene constraint: LOEUF 0.483 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 69.12 · 1 PDB

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

Similar variants

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
EHF p.Arg293Leu 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-val128 (accessed [today's date]).

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