Is LRMDA p.Ser198= (c.594T>C) pathogenic?

LRMDA p.Ser198= (c.594T>C) is classified Likely benign in LRMDA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). Very rare (popmax 0.00134%, afr).

How common is LRMDA p.Ser198= (c.594T>C) in the general population?

LRMDA p.Ser198= (c.594T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

LRMDA p.Ser198=

c.594T>C · rs200571917 · VCV2908816

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.28	GERP -4.2, phastCons 1
Overall
CADD	8.108	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,862 alleles

Overall 6.2e-05% 1/1,613,902 alleles · very rare exomes 0/1,461,868 · genomes 1/152,034 · joint denominator

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.Ser198=
Coding: c.594T>C
MANE Select: NM_001305581
dbSNP: rs200571917
Type: single nucleotide variant
Location: chr10:76324478 (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.Ser198Gly 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-ser198 (accessed [today's date]).

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