Is LRMDA p.Pro182= (c.546G>A) pathogenic?

LRMDA p.Pro182= (c.546G>A) is classified Likely benign in LRMDA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). Rare (popmax 0.104%, sas).

How common is LRMDA p.Pro182= (c.546G>A) in the general population?

LRMDA p.Pro182= (c.546G>A) is rare (popmax 0.104%, sas) (gnomAD).

LRMDA p.Pro182=

c.546G>A · rs775067979 · VCV1905349

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.104%, sas)

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 -7.8	GERP -5.2
Overall
CADD	0.054	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.104% South Asian · 95/91,060 alleles

Filtering AF 0.0873% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.081%

Overall 0.0075% 121/1,613,882 alleles · rare exomes 118/1,461,876 · genomes 3/152,006 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.104%	959
Middle Eastern	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00161%	62,106

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: LRMDA
Protein: p.Pro182=
Coding: c.546G>A
MANE Select: NM_001305581
dbSNP: rs775067979
Type: single nucleotide variant
Location: chr10:76324430 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.40

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

Similar variants

LRMDA p.Pro182Leu Uncertain significance ★ ⚠ same residue
LRMDA p.Arg184Cys Uncertain significance ★★ ⚠ same type
LRMDA p.Arg207His Uncertain significance ★★ ⚠ same type
LRMDA p.Met166Thr Uncertain significance ★★ ⚠ same type
LRMDA p.Tyr129Cys Uncertain significance ★★ ⚠ same type
LRMDA c.132-253009C>T Benign/Likely benign ★★ same type
LRMDA c.398+31A>C Benign ★★ same type
LRMDA c.516+53C>T Benign ★★ 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/lrmda-p-pro182 (accessed [today's date]).

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