Is EHHADH p.Thr136Ser (c.407C>G) pathogenic?

EHHADH p.Thr136Ser (c.407C>G) is classified Uncertain significance in EHHADH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-20). AlphaMissense: ambiguous (0.3664); Absent from gnomAD v4.1.

How common is EHHADH p.Thr136Ser (c.407C>G) in the general population?

EHHADH p.Thr136Ser (c.407C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EHHADH p.Thr136Ser (c.407C>G)?

AlphaMissense predicts ambiguous (score 0.3664) — an in-silico prediction, not a clinical call.

EHHADH p.Thr136Ser

c.407C>G · VCV3507428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3664 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3664	ambiguous
REVEL	0.43	indeterminate
SaProt	LLR -10.09	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.44 · regional, not allelic
Overall
CADD	23.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EHHADH
Protein: p.Thr136Ser
Coding: c.407C>G
MANE Select: NM_001966
Type: single nucleotide variant
Location: chr3:185229488 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.07
Residue 136: the 'enoyl-coa hydratase / isomerase' region

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-thr136ser (accessed [today's date]).

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