Is PDHA1 p.His367Pro (c.1100A>C) pathogenic?

PDHA1 p.His367Pro (c.1100A>C) is classified Pathogenic/Likely pathogenic in PDHA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-06). AlphaMissense: likely pathogenic (0.7532); Absent from gnomAD v4.1.

How common is PDHA1 p.His367Pro (c.1100A>C) in the general population?

PDHA1 p.His367Pro (c.1100A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDHA1 p.His367Pro (c.1100A>C)?

AlphaMissense predicts likely pathogenic (score 0.7532) — an in-silico prediction, not a clinical call.

PDHA1 p.His367Pro

c.1100A>C · rs1131691584 · VCV429771

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7532 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7532	likely pathogenic ✓ concordant with ClinVar
REVEL	0.705	pathogenic-leaning
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 711 bp · p 0.5 · regional, not allelic
Overall
CADD	23.6	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: PDHA1
Protein: p.His367Pro
Coding: c.1100A>C
MANE Select: NM_000284
dbSNP: rs1131691584
Type: single nucleotide variant
Location: chrX:19359580 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 9 PDB
Residue 367: a β-strand

Full PDHA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDHA1 p.His367Tyr Likely benign ★ same residue
PDHA1 p.His367Arg Likely pathogenic same residue
PDHA1 p.His367Leu Pathogenic same residue
PDHA1 p.His367= Uncertain significance same residue
PDHA1 p.Ala169Val Pathogenic ★★★ same type
PDHA1 p.Arg304Ter Pathogenic ★★★ same type
PDHA1 p.Arg378Cys Pathogenic ★★★ ⚠ same type
PDHA1 p.Arg72Cys Likely pathogenic ★★★ 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/pdha1-p-his367pro (accessed [today's date]).

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