Is LAMA4 p.Ser577Phe (c.1730C>T) pathogenic?

LAMA4 p.Ser577Phe (c.1730C>T) is classified Uncertain significance in LAMA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-13). AlphaMissense: likely benign (0.1605); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with LAMA4 p.Ser577Phe (c.1730C>T)?

LAMA4 p.Ser577Phe (c.1730C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LAMA4 p.Ser577Phe (c.1730C>T) in the general population?

LAMA4 p.Ser577Phe (c.1730C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LAMA4 p.Ser577Phe (c.1730C>T)?

AlphaMissense predicts likely benign (score 0.1605) — an in-silico prediction, not a clinical call.

LAMA4 p.Ser577Phe

c.1730C>T · VCV3866202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1605 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1605	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 132 kb · p 0.046 · regional, not allelic
Overall
CADD	23.4	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: LAMA4
Protein: p.Ser577Phe
Coding: c.1730C>T
MANE Select: NM_001105206
Type: single nucleotide variant
Location: chr6:112158819 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.75
Residue 577: the 'domain ii and i' region

Full LAMA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMA4 p.Ser577Pro Uncertain significance ★ ⚠ same residue
LAMA4 c.1077+4C>T Uncertain significance ★★ same condition
LAMA4 c.718+5A>G Uncertain significance ★★ same condition
LAMA4 c.815-2A>G Uncertain significance ★★ same condition
LAMA4 c.966+4C>G Uncertain significance ★★ same condition
LAMA4 c.966+4C>T Uncertain significance ★★ same condition
LAMA4 c.967-5T>G Uncertain significance ★★ same condition
LAMA4 p.Ala1009Asp 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/lama4-p-ser577phe (accessed [today's date]).

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