Is AP1M1 p.Val342Met (c.1024G>A) pathogenic?

AP1M1 p.Val342Met (c.1024G>A) is classified Uncertain significance in AP1M1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely benign (0.186); Ultra-rare (popmax 0.0494%, sas).

How common is AP1M1 p.Val342Met (c.1024G>A) in the general population?

AP1M1 p.Val342Met (c.1024G>A) is ultra-rare (popmax 0.0494%, sas) (gnomAD).

What do computational predictors say about AP1M1 p.Val342Met (c.1024G>A)?

AlphaMissense predicts likely benign (score 0.186) — an in-silico prediction, not a clinical call.

AP1M1 p.Val342Met

c.1024G>A · VCV3922167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.186 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.186	likely benign
REVEL	0.287	benign-leaning
SaProt	LLR -10.52	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP -0.46, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 35 kb · p 1.4e-14 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 0.0494% South Asian · 45/91,074 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.00353% 57/1,614,042 alleles · ultra-rare exomes 52/1,461,800 · genomes 5/152,242 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0494%	2,024
African / African-American	0.008%	12,506
East Asian	0.00223%	44,864
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000339%	294,989

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: AP1M1
Protein: p.Val342Met
Coding: c.1024G>A
MANE Select: NM_032493
Type: single nucleotide variant
Location: chr19:16228905 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.41
Residue 342: the mhd domain

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-val342met (accessed [today's date]).

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