Is POLH p.Val367Ala (c.1100T>C) pathogenic?

POLH p.Val367Ala (c.1100T>C) is classified Likely benign in POLH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely benign (0.0526); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with POLH p.Val367Ala (c.1100T>C)?

POLH p.Val367Ala (c.1100T>C) is associated with Inborn genetic diseases (ClinVar).

How common is POLH p.Val367Ala (c.1100T>C) in the general population?

POLH p.Val367Ala (c.1100T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about POLH p.Val367Ala (c.1100T>C)?

AlphaMissense predicts likely benign (score 0.0526) — an in-silico prediction, not a clinical call.

POLH p.Val367Ala

c.1100T>C · rs1344022511 · VCV2544882

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0526 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0526	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.55	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 -7.5	GERP -3.6
Regional constraint	o/e 0.89	unconstrained · MANE · 32 kb · p 0.00093 · regional, not allelic
Overall
CADD	0.493	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: POLH
Protein: p.Val367Ala
Coding: c.1100T>C
MANE Select: NM_006502
dbSNP: rs1344022511
Type: single nucleotide variant
Location: chr6:43610579 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 241 PDB
Residue 367: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

POLH p.Ala562Pro Uncertain significance ★★ ⚠ same condition
POLH p.Leu567Ser Uncertain significance ★★ ⚠ same condition
POLH p.Thr502Ile Uncertain significance ★★ ⚠ same condition
POLH p.Ala202Glu Uncertain significance ★ ⚠ same condition
POLH p.Ala35Val Conflicting classifications of pathogenicity ★ ⚠ same condition
POLH p.Ala386Pro Uncertain significance ★ ⚠ same condition
POLH p.Ala488Val Uncertain significance ★ ⚠ same condition
POLH p.Ala49Val Uncertain significance ★ ⚠ same condition

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/polh-p-val367ala (accessed [today's date]).

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