Is EHD1 p.Ala273= (c.819C>G) pathogenic?

EHD1 p.Ala273= (c.819C>G) is classified Benign in EHD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-10). Common (popmax 5.18%, afr) — too common for a highly-penetrant pathogenic allele.

EHD1 p.Ala273=

Q: How common is EHD1 p.Ala273= (c.819C>G) in the general population?

EHD1 p.Ala273= (c.819C>G) is common (popmax 5.18%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.819C>G · rs61738612 · VCV783618

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.18%, afr) — too common for a highly-penetrant pathogenic allele

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 -7.4	GERP -4.3
Overall
CADD	2.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.18% African / African-American · 3,884/75,014 alleles

Filtering AF 5.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.99%

Overall 0.292% 4,712/1,614,064 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.18%	19
Admixed American	0.427%	234
Remaining individualsnot grpmax-eligible	0.37%	271
Middle Eastern	0.132%	758
Finnishnot grpmax-eligible	0.0328%	3,045
European (non-Finnish)	0.0258%	3,882
South Asian	0.00878%	11,386

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: EHD1
Protein: p.Ala273=
Coding: c.819C>G
MANE Select: NM_006795
dbSNP: rs61738612
Type: single nucleotide variant
Location: chr11:64860020 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 89.65 · 5 PDB
Residue 273: the dynamin-type g domain

Full EHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EHD1 p.Gly464= Benign ★★ same type
EHD1 p.Leu114= Benign ★★ same type
EHD1 p.Leu187= Benign ★★ same type
EHD1 p.Ala304Gly Uncertain significance ★ ⚠ same type
EHD1 p.Ala308Thr Uncertain significance ★ ⚠ same type
EHD1 p.Ala373Val Uncertain significance ★ ⚠ same type
EHD1 p.Ala413Val Uncertain significance ★ ⚠ same type
EHD1 p.Ala465Thr 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/ehd1-p-ala273 (accessed [today's date]).

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