Is LAMB3 p.Phe4Leu (c.10T>C) pathogenic?

LAMB3 p.Phe4Leu (c.10T>C) is classified Conflicting classifications of pathogenicity in LAMB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-11-12). AlphaMissense: likely benign (0.1288); Rare (popmax 0.123%, afr); Associated with Inborn genetic diseases.

What condition is associated with LAMB3 p.Phe4Leu (c.10T>C)?

LAMB3 p.Phe4Leu (c.10T>C) is associated with Inborn genetic diseases (ClinVar).

How common is LAMB3 p.Phe4Leu (c.10T>C) in the general population?

LAMB3 p.Phe4Leu (c.10T>C) is rare (popmax 0.123%, afr) (gnomAD).

What do computational predictors say about LAMB3 p.Phe4Leu (c.10T>C)?

AlphaMissense predicts likely benign (score 0.1288) — an in-silico prediction, not a clinical call.

LAMB3 p.Phe4Leu

c.10T>C · rs116218572 · VCV2201625

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1288 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.123%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1288	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -3.87	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 0.07	GERP -2.9
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.27 · regional, not allelic
Overall
CADD	6.676	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 0.123% African / African-American · 92/75,058 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0948%

Overall 0.00787% 127/1,614,194 alleles · rare exomes 64/1,461,872 · genomes 63/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.123%	816
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.005%	20,011
European (non-Finnish)	0.00212%	47,200

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: LAMB3
Protein: p.Phe4Leu
Coding: c.10T>C
MANE Select: NM_000228
dbSNP: rs116218572
Type: single nucleotide variant
Location: chr1:209650935 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55

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.Phe4= Likely benign ★ same residue
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

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-phe4leu (accessed [today's date]).

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