Is LRMDA p.Ala148= (c.444C>T) pathogenic?

LRMDA p.Ala148= (c.444C>T) is classified Likely benign in LRMDA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). Ultra-rare (popmax 0.0132%, nfe).

How common is LRMDA p.Ala148= (c.444C>T) in the general population?

LRMDA p.Ala148= (c.444C>T) is ultra-rare (popmax 0.0132%, nfe) (gnomAD).

LRMDA p.Ala148=

c.444C>T · rs768684891 · VCV1933679

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, nfe)

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 -0.64	GERP -2.4
Overall
CADD	7.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% European (non-Finnish) · 156/1,179,990 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.00991% 160/1,613,836 alleles · ultra-rare exomes 156/1,461,840 · genomes 4/151,996 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0132%	7,564
Remaining individualsnot grpmax-eligible	0.0032%	31,238
African / African-American	0.00267%	37,429

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.Ala148=
Coding: c.444C>T
MANE Select: NM_001305581
dbSNP: rs768684891
Type: single nucleotide variant
Location: chr10:76058711 (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.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
LRMDA c.601+18T>G Likely 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-ala148 (accessed [today's date]).

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