Is EHHADH p.Ile41Val (c.121A>G) pathogenic?

EHHADH p.Ile41Val (c.121A>G) is classified Benign in EHHADH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-18). AlphaMissense: likely benign (0.079); Low-frequency (popmax 1.35%, afr).

How common is EHHADH p.Ile41Val (c.121A>G) in the general population?

EHHADH p.Ile41Val (c.121A>G) is low-frequency (popmax 1.35%, afr) (gnomAD).

What do computational predictors say about EHHADH p.Ile41Val (c.121A>G)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

EHHADH p.Ile41Val

c.121A>G · rs78790730 · VCV733114

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -3.31	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 0.006	GERP -3.1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.44 · regional, not allelic
Overall
CADD	0.454	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 1.35% African / African-American · 1,017/75,056 alleles

Filtering AF 1.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.26%

Overall 0.0702% 1,133/1,614,072 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.35%	74
Remaining individualsnot grpmax-eligible	0.088%	1,136
Admixed American	0.0833%	1,200
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,353
European (non-Finnish)	0.000593%	168,566

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: EHHADH
Protein: p.Ile41Val
Coding: c.121A>G
MANE Select: NM_001966
dbSNP: rs78790730
Type: single nucleotide variant
Location: chr3:185248471 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.07
Residue 41: the 'enoyl-coa hydratase / isomerase' region; a UniProt-annotated variant site (in)

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

Similar variants

EHHADH p.Ala10Thr Uncertain significance ★★ ⚠ same type
EHHADH p.Ala118Val Uncertain significance ★★ ⚠ same type
EHHADH p.Ala294Val Uncertain significance ★★ ⚠ same type
EHHADH p.Arg183Gly Uncertain significance ★★ ⚠ same type
EHHADH p.Arg633Cys Uncertain significance ★★ ⚠ same type
EHHADH p.Arg64Cys Uncertain significance ★★ ⚠ same type
EHHADH p.Asn629Ser Uncertain significance ★★ ⚠ same type
EHHADH p.Asp42Glu 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/ehhadh-p-ile41val (accessed [today's date]).

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