Is LAMA2 p.Pro855Arg (c.2564C>G) pathogenic?

LAMA2 p.Pro855Arg (c.2564C>G) is classified Uncertain significance in LAMA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-18). AlphaMissense: likely pathogenic (0.8396); Very rare (popmax 0.00446%, eas).

How common is LAMA2 p.Pro855Arg (c.2564C>G) in the general population?

LAMA2 p.Pro855Arg (c.2564C>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about LAMA2 p.Pro855Arg (c.2564C>G)?

AlphaMissense predicts likely pathogenic (score 0.8396) — an in-silico prediction, not a clinical call.

LAMA2 p.Pro855Arg

c.2564C>G · rs754714449 · VCV546367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8396 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.8396	likely pathogenic
REVEL	0.695	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 351 kb · p 0.83 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,876 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000991% 16/1,613,870 alleles · very rare exomes 16/1,461,672 · genomes 0/152,198 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,438
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.0011%	90,758

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: LAMA2
Protein: p.Pro855Arg
Coding: c.2564C>G
MANE Select: NM_000426
dbSNP: rs754714449
Type: single nucleotide variant
Location: chr6:129287873 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 855: the laminin egf-like 7 domain; a UniProt-annotated variant site (in mdc1a); a UniProt-annotated variant site (in lgmdr23)

Full LAMA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LAMA2 p.Pro855Leu Uncertain significance ★★ ⚠ same residue
LAMA2 p.Pro855= Likely benign ★ same residue
LAMA2 c.1028-1G>A Likely pathogenic ★★ same type
LAMA2 c.112+1G>A Pathogenic/Likely pathogenic ★★ same type
LAMA2 c.112+2T>C Pathogenic ★★ same type
LAMA2 c.1306+2T>G Pathogenic/Likely pathogenic ★★ same type
LAMA2 c.1467+1G>A Pathogenic/Likely pathogenic ★★ same type
LAMA2 c.1467+2T>C Pathogenic/Likely pathogenic ★★ 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/lama2-p-pro855arg (accessed [today's date]).

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