Is LRRTM3 p.Ser303Phe (c.908C>T) pathogenic?

LRRTM3 p.Ser303Phe (c.908C>T) is classified Uncertain significance in LRRTM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely pathogenic (0.5978); Absent from gnomAD v4.1.

How common is LRRTM3 p.Ser303Phe (c.908C>T) in the general population?

LRRTM3 p.Ser303Phe (c.908C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRRTM3 p.Ser303Phe (c.908C>T)?

AlphaMissense predicts likely pathogenic (score 0.5978) — an in-silico prediction, not a clinical call.

LRRTM3 p.Ser303Phe

c.908C>T · VCV4101046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5978	likely pathogenic
REVEL	0.558	indeterminate
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 826 bp · p 1.8e-08 · regional, not allelic
Overall
CADD	29.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LRRTM3
Protein: p.Ser303Phe
Coding: c.908C>T
MANE Select: NM_178011
Type: single nucleotide variant
Location: chr10:66927824 (GRCh38)
Gene constraint: LOEUF 0.721 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.23

Full LRRTM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LRRTM3 p.Ala223Val Uncertain significance ★ ⚠ same type
LRRTM3 p.Ala372Ser Uncertain significance ★ ⚠ same type
LRRTM3 p.Ala401Ser Uncertain significance ★ ⚠ same type
LRRTM3 p.Ala581Thr Uncertain significance ★ ⚠ same type
LRRTM3 p.Arg109Cys Uncertain significance ★ ⚠ same type
LRRTM3 p.Arg109His Uncertain significance ★ ⚠ same type
LRRTM3 p.Arg282Leu Uncertain significance ★ ⚠ same type
LRRTM3 p.Arg444Leu 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/lrrtm3-p-ser303phe (accessed [today's date]).

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