Is LAMTOR3 p.Pro31Ala (c.91C>G) pathogenic?

LAMTOR3 p.Pro31Ala (c.91C>G) is classified Uncertain significance in LAMTOR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-16). AlphaMissense: likely pathogenic (0.7673); Very rare (popmax 0.000867%, nfe).

How common is LAMTOR3 p.Pro31Ala (c.91C>G) in the general population?

LAMTOR3 p.Pro31Ala (c.91C>G) is very rare (popmax 0.000867%, nfe) (gnomAD).

What do computational predictors say about LAMTOR3 p.Pro31Ala (c.91C>G)?

AlphaMissense predicts likely pathogenic (score 0.7673) — an in-silico prediction, not a clinical call.

LAMTOR3 p.Pro31Ala

c.91C>G · rs1448741915 · VCV2546554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7673 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000867%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7673	likely pathogenic
REVEL	0.685	pathogenic-leaning
SaProt	LLR -3.49	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,848 bp · p 0.76 · regional, not allelic
Overall
CADD	27.0	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 0.000867% European (non-Finnish) · 10/1,153,046 alleles

Filtering AF 0.000439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00032%

Overall 0.000639% 10/1,565,160 alleles · very rare exomes 10/1,413,200 · genomes 0/151,960 · joint denominator

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: LAMTOR3
Protein: p.Pro31Ala
Coding: c.91C>G
MANE Select: NM_021970
dbSNP: rs1448741915
Type: single nucleotide variant
Location: chr4:99887308 (GRCh38)
Gene constraint: LOEUF 1.64 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.53 · 25 PDB
Residue 31: a β-strand

Full LAMTOR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LAMTOR3 p.Ala21Gly Uncertain significance ★ same type
LAMTOR3 p.Arg46Gln Uncertain significance ★ ⚠ same type
LAMTOR3 p.Arg85His Uncertain significance ★ ⚠ same type
LAMTOR3 p.Asn39Ser Uncertain significance ★ ⚠ same type
LAMTOR3 p.Glu109Lys Uncertain significance ★ ⚠ same type
LAMTOR3 p.His43Gln Uncertain significance ★ ⚠ same type
LAMTOR3 p.Ile72Met Uncertain significance ★ same type
LAMTOR3 p.Ile93Leu 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/lamtor3-p-pro31ala (accessed [today's date]).

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