Is LAMB3 p.Ser733Phe (c.2198C>T) pathogenic?

LAMB3 p.Ser733Phe (c.2198C>T) is classified Uncertain significance in LAMB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.1529); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with LAMB3 p.Ser733Phe (c.2198C>T)?

LAMB3 p.Ser733Phe (c.2198C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LAMB3 p.Ser733Phe (c.2198C>T) in the general population?

LAMB3 p.Ser733Phe (c.2198C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about LAMB3 p.Ser733Phe (c.2198C>T)?

AlphaMissense predicts likely benign (score 0.1529) — an in-silico prediction, not a clinical call.

LAMB3 p.Ser733Phe

c.2198C>T · rs768646871 · VCV3117621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1529 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1529	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -10.15	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.8, phastCons 0.94
Regional constraint	o/e 0.97	unconstrained · MANE · 36 kb · p 0.27 · regional, not allelic
Overall
CADD	18.61	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 0.004% African / African-American · 3/75,080 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000434% 7/1,614,222 alleles · very rare exomes 7/1,461,852 · genomes 0/152,370 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,027
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Admixed American	0.00167%	60,032
European (non-Finnish)	8.47e-05%	1,180,034

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.Ser733Phe
Coding: c.2198C>T
MANE Select: NM_000228
dbSNP: rs768646871
Type: single nucleotide variant
Location: chr1:209623665 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 733: the 'domain ii' 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.Ser733= 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-ser733phe (accessed [today's date]).

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