Is EHHADH p.Pro502Arg (c.1505C>G) pathogenic?

EHHADH p.Pro502Arg (c.1505C>G) is classified Uncertain significance in EHHADH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-19). AlphaMissense: likely pathogenic (0.8156); Rare (popmax 0.315%, sas).

How common is EHHADH p.Pro502Arg (c.1505C>G) in the general population?

EHHADH p.Pro502Arg (c.1505C>G) is rare (popmax 0.315%, sas) (gnomAD).

What do computational predictors say about EHHADH p.Pro502Arg (c.1505C>G)?

AlphaMissense predicts likely pathogenic (score 0.8156) — an in-silico prediction, not a clinical call.

EHHADH p.Pro502Arg

c.1505C>G · rs551915910 · VCV598090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8156 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.315%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8156	likely pathogenic
REVEL	0.807	moderately pathogenic-leaning
SaProt	LLR -13.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.44 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.315% South Asian · 287/91,078 alleles

Filtering AF 0.285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.273%

Overall 0.0201% 324/1,614,100 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.315%	317
Middle Eastern	0.181%	551
Remaining individualsnot grpmax-eligible	0.024%	4,167
European (non-Finnish)	0.000932%	107,275

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.Pro502Arg
Coding: c.1505C>G
MANE Select: NM_001966
dbSNP: rs551915910
Type: single nucleotide variant
Location: chr3:185192893 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.07
Residue 502: the '3-hydroxyacyl-coa dehydrogenase' region

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

Similar variants

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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-pro502arg (accessed [today's date]).

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