Is LAP3 p.Val485Met (c.1453G>A) pathogenic?

LAP3 p.Val485Met (c.1453G>A) is classified Uncertain significance in LAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely pathogenic (0.8391); Very rare (popmax 0.00167%, amr).

How common is LAP3 p.Val485Met (c.1453G>A) in the general population?

LAP3 p.Val485Met (c.1453G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about LAP3 p.Val485Met (c.1453G>A)?

AlphaMissense predicts likely pathogenic (score 0.8391) — an in-silico prediction, not a clinical call.

LAP3 p.Val485Met

c.1453G>A · VCV3866430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8391 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8391	likely pathogenic
REVEL	0.473	indeterminate
SaProt	LLR -9.03	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 30 kb · p 0.086 · regional, not allelic
Overall
CADD	27.3	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 0.00167% Admixed American · 1/59,988 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,614,106 alleles · very rare exomes 8/1,461,820 · genomes 0/152,286 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,988
European (non-Finnish)	0.000593%	168,574

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.Val485Met
Coding: c.1453G>A
MANE Select: NM_015907
Type: single nucleotide variant
Location: chr4:17607482 (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-val485met (accessed [today's date]).

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