Is LEMD3 p.Ser95= (c.285G>A) pathogenic?

LEMD3 p.Ser95= (c.285G>A) is classified Likely benign in LEMD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). Very rare (popmax 9.07e-05%, nfe).

How common is LEMD3 p.Ser95= (c.285G>A) in the general population?

LEMD3 p.Ser95= (c.285G>A) is very rare (popmax 9.07e-05%, nfe) (gnomAD).

LEMD3 p.Ser95=

c.285G>A · rs946036522 · VCV1910614

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 9.07e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	7.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.07e-05% European (non-Finnish) · 1/1,102,098 alleles

Overall 0.00145% 21/1,452,044 alleles · very rare exomes 19/1,300,226 · genomes 2/151,818 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0757%	1,321
Remaining individualsnot grpmax-eligible	0.0054%	18,519
European (non-Finnish)grpmax	9.07e-05%	1,102,098

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: LEMD3
Protein: p.Ser95=
Coding: c.285G>A
MANE Select: NM_014319
dbSNP: rs946036522
Type: single nucleotide variant
Location: chr12:65169881 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.40 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.07 · 3 PDB

Full LEMD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LEMD3 p.Ser95Ala Likely benign ★ same residue
LEMD3 p.Arg537Ter Pathogenic ★★ same type
LEMD3 p.Arg625Ter Pathogenic ★★ same type
LEMD3 p.Arg655Ter Pathogenic/Likely pathogenic ★★ same type
LEMD3 p.Arg678Ter Pathogenic/Likely pathogenic ★★ same type
LEMD3 p.Arg735Ter Pathogenic ★★ same type
LEMD3 p.Glu601Ter Pathogenic/Likely pathogenic ★★ same type
LEMD3 p.Tyr441Ter 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/lemd3-p-ser95 (accessed [today's date]).

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