Is LAMB3 p.Ser950Phe (c.2849C>T) pathogenic?

LAMB3 p.Ser950Phe (c.2849C>T) is classified Uncertain significance in LAMB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-20). AlphaMissense: likely benign (0.2139); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LAMB3 p.Ser950Phe (c.2849C>T)?

LAMB3 p.Ser950Phe (c.2849C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LAMB3 p.Ser950Phe (c.2849C>T) in the general population?

LAMB3 p.Ser950Phe (c.2849C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LAMB3 p.Ser950Phe (c.2849C>T)?

AlphaMissense predicts likely benign (score 0.2139) — an in-silico prediction, not a clinical call.

LAMB3 p.Ser950Phe

c.2849C>T · VCV4859121

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2139 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2139	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -9.48	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 8.5	GERP 0.64, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.27 · regional, not allelic
Overall
CADD	25.5	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

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: LAMB3
Protein: p.Ser950Phe
Coding: c.2849C>T
MANE Select: NM_000228
Type: single nucleotide variant
Location: chr1:209618512 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 950: the 'domain i' region

Full LAMB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMB3 p.Ala1071Thr Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala1145Val Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala330Thr Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala330Val Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala590Val Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala825Thr Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala832Val Uncertain significance ★★ ⚠ same condition
LAMB3 p.Ala855Gly Uncertain significance ★★ ⚠ same condition

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/lamb3-p-ser950phe (accessed [today's date]).

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