Is LAP3 p.Ala30Val (c.89C>T) pathogenic?

LAP3 p.Ala30Val (c.89C>T) is classified Uncertain significance in LAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely benign (0.1134); Very rare (popmax 0.00831%, nfe).

How common is LAP3 p.Ala30Val (c.89C>T) in the general population?

LAP3 p.Ala30Val (c.89C>T) is very rare (popmax 0.00831%, nfe) (gnomAD).

What do computational predictors say about LAP3 p.Ala30Val (c.89C>T)?

AlphaMissense predicts likely benign (score 0.1134) — an in-silico prediction, not a clinical call.

LAP3 p.Ala30Val

c.89C>T · VCV3537257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1134 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00831%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1134	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.16	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	GERP -0.4, phastCons 0.9
Regional constraint	o/e 0.93	unconstrained · MANE · 30 kb · p 0.086 · regional, not allelic
Overall
CADD	19.85	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 0.00831% European (non-Finnish) · 96/1,155,318 alleles

Filtering AF 0.00695% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00646%

Overall 0.00627% 98/1,563,254 alleles · very rare exomes 94/1,411,046 · genomes 4/152,208 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00831%	12,035
Remaining individualsnot grpmax-eligible	0.00165%	60,432
African / African-American	0.00136%	73,314

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.Ala30Val
Coding: c.89C>T
MANE Select: NM_015907
Type: single nucleotide variant
Location: chr4:17577554 (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.Ala30Thr Uncertain significance ★ ⚠ same residue
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.Ala320Thr 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-ala30val (accessed [today's date]).

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