Is LAMB1 p.Phe588= (c.1764C>T) pathogenic?

LAMB1 p.Phe588= (c.1764C>T) is classified Likely benign in LAMB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). Very rare (popmax 0.005%, amr).

How common is LAMB1 p.Phe588= (c.1764C>T) in the general population?

LAMB1 p.Phe588= (c.1764C>T) is very rare (popmax 0.005%, amr) (gnomAD).

LAMB1 p.Phe588=

c.1764C>T · rs34450895 · VCV732321

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.3	GERP -3.6
Overall
CADD	4.318	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,988 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00124% 20/1,613,896 alleles · very rare exomes 16/1,461,742 · genomes 4/152,154 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00781%	12,802
Admixed Americangrpmax	0.005%	19,996
East Asian	0.00223%	44,894
South Asian	0.0022%	45,540
African / African-American	0.00133%	74,920
European (non-Finnish)	0.000678%	147,490

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: LAMB1
Protein: p.Phe588=
Coding: c.1764C>T
MANE Select: NM_002291
dbSNP: rs34450895
Type: single nucleotide variant
Location: chr7:107962998 (GRCh38)
Gene constraint: LOEUF 0.601 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.99 · 3 PDB
Residue 588: the laminin iv type b domain

Full LAMB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LAMB1 c.4188+1G>C Pathogenic/Likely pathogenic ★★ same type
LAMB1 p.Arg397Ter Pathogenic ★★ same type
LAMB1 p.Gln577Ter Pathogenic ★★ same type
LAMB1 c.1985+5G>T Uncertain significance ★★ same type
LAMB1 c.4746-3C>A Uncertain significance ★★ same type
LAMB1 p.Ala1069Val Uncertain significance ★★ ⚠ same type
LAMB1 p.Ala1239Thr Uncertain significance ★★ ⚠ same type
LAMB1 p.Ala1331Gly 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/lamb1-p-phe588 (accessed [today's date]).

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