Is APEH p.Pro472Ala (c.1414C>G) pathogenic?

APEH p.Pro472Ala (c.1414C>G) is classified Uncertain significance in APEH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.0547); Absent from gnomAD v4.1.

How common is APEH p.Pro472Ala (c.1414C>G) in the general population?

APEH p.Pro472Ala (c.1414C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APEH p.Pro472Ala (c.1414C>G)?

AlphaMissense predicts likely benign (score 0.0547) — an in-silico prediction, not a clinical call.

APEH p.Pro472Ala

c.1414C>G · VCV4641615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0547 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0547	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -6.68	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 2.7	GERP 1.2, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 8,937 bp · p 0.011 · regional, not allelic
Overall
CADD	18.95	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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: APEH
Protein: p.Pro472Ala
Coding: c.1414C>G
MANE Select: NM_001640
Type: single nucleotide variant
Location: chr3:49681215 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58

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

Similar variants

APEH p.Pro472Leu Uncertain significance ★ ⚠ same residue
APEH p.Arg107Cys Uncertain significance ★ ⚠ same type
APEH p.Arg128Gly Uncertain significance ★ ⚠ same type
APEH p.Arg278Cys Uncertain significance ★ ⚠ same type
APEH p.Arg278His Uncertain significance ★ ⚠ same type
APEH p.Arg306Trp Uncertain significance ★ ⚠ same type
APEH p.Arg313Leu Uncertain significance ★ ⚠ same type
APEH p.Arg383Cys 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/apeh-p-pro472ala (accessed [today's date]).

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