Is AP1M1 p.Val15Ala (c.44T>C) pathogenic?

AP1M1 p.Val15Ala (c.44T>C) is classified Uncertain significance in AP1M1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: ambiguous (0.5496); Absent from gnomAD v4.1.

How common is AP1M1 p.Val15Ala (c.44T>C) in the general population?

AP1M1 p.Val15Ala (c.44T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP1M1 p.Val15Ala (c.44T>C)?

AlphaMissense predicts ambiguous (score 0.5496) — an in-silico prediction, not a clinical call.

AP1M1 p.Val15Ala

c.44T>C · VCV4641425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5496 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5496	ambiguous
REVEL	0.231	benign-leaning
SaProt	LLR -7.61	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP -0.47, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 35 kb · p 1.4e-14 · regional, not allelic
Overall
CADD	23.9	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: AP1M1
Protein: p.Val15Ala
Coding: c.44T>C
MANE Select: NM_032493
Type: single nucleotide variant
Location: chr19:16203460 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.41

Full AP1M1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP1M1 p.Ala75Val Uncertain significance ★ ⚠ same type
AP1M1 p.Arg104Trp Uncertain significance ★ ⚠ same type
AP1M1 p.Arg148Gln Uncertain significance ★ ⚠ same type
AP1M1 p.Arg191Cys Uncertain significance ★ ⚠ same type
AP1M1 p.Arg22Cys Uncertain significance ★ ⚠ same type
AP1M1 p.Arg22His Uncertain significance ★ ⚠ same type
AP1M1 p.Arg246His Uncertain significance ★ ⚠ same type
AP1M1 p.Arg410His 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/ap1m1-p-val15ala (accessed [today's date]).

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