Is EHF p.Asp145= (c.435C>T) pathogenic?

EHF p.Asp145= (c.435C>T) is classified Likely benign in EHF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). Ultra-rare (popmax 0.0165%, mid).

How common is EHF p.Asp145= (c.435C>T) in the general population?

EHF p.Asp145= (c.435C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

EHF p.Asp145=

c.435C>T · VCV3843996

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 1	GERP -4.9, phastCons 0.99
Overall
CADD	12.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.0039% 63/1,613,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,480
Middle Easterngrpmax	0.0165%	6,060
East Asian	0.00669%	14,959
Admixed American	0.005%	20,005
Remaining individualsnot grpmax-eligible	0.0048%	20,833
South Asian	0.00329%	30,354
African / African-American	0.00267%	37,504
European (non-Finnish)	0.00237%	42,138

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp145=
Coding: c.435C>T
MANE Select: NM_012153
Type: single nucleotide variant
Location: chr11:34651570 (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 p.Asp145Glu Likely benign ★ 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-asp145 (accessed [today's date]).

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