Is LAP3 p.Met32Arg (c.95T>G) pathogenic?

LAP3 p.Met32Arg (c.95T>G) is classified Uncertain significance in LAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: likely benign (0.1144); Very rare (popmax 0.00574%, nfe).

How common is LAP3 p.Met32Arg (c.95T>G) in the general population?

LAP3 p.Met32Arg (c.95T>G) is very rare (popmax 0.00574%, nfe) (gnomAD).

What do computational predictors say about LAP3 p.Met32Arg (c.95T>G)?

AlphaMissense predicts likely benign (score 0.1144) — an in-silico prediction, not a clinical call.

LAP3 p.Met32Arg

c.95T>G · rs762408178 · VCV2270547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00574%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1144	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -6.29	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 7.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 30 kb · p 0.086 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.00574% European (non-Finnish) · 66/1,150,312 alleles

Filtering AF 0.00463% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00422%

Overall 0.00437% 68/1,554,632 alleles · very rare exomes 64/1,402,556 · genomes 4/152,076 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00574%	17,429
African / African-American	0.00274%	36,432

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: LAP3
Protein: p.Met32Arg
Coding: c.95T>G
MANE Select: NM_015907
dbSNP: rs762408178
Type: single nucleotide variant
Location: chr4:17577560 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.18

Full LAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LAP3 p.Ala105Ser Uncertain significance ★ ⚠ same type
LAP3 p.Ala148Thr Uncertain significance ★ ⚠ same type
LAP3 p.Ala151Ser Uncertain significance ★ ⚠ same type
LAP3 p.Ala175Thr Uncertain significance ★ ⚠ same type
LAP3 p.Ala199Gly Uncertain significance ★ same type
LAP3 p.Ala244Thr Uncertain significance ★ ⚠ same type
LAP3 p.Ala30Thr Uncertain significance ★ ⚠ same type
LAP3 p.Ala30Val 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/lap3-p-met32arg (accessed [today's date]).

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