Is GSDMD p.Ser3= (c.9G>T) pathogenic?

GSDMD p.Ser3= (c.9G>T) is classified Benign in GSDMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-04). Common (popmax 9.04%, afr) — too common for a highly-penetrant pathogenic allele.

GSDMD p.Ser3=

Q: How common is GSDMD p.Ser3= (c.9G>T) in the general population?

GSDMD p.Ser3= (c.9G>T) is common (popmax 9.04%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9G>T · rs7840446 · VCV781163

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.04%, afr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3.3
Overall
CADD	0.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.04% African / African-American · 6,739/74,546 alleles

Filtering AF 8.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.79%

Overall 0.506% 8,155/1,610,978 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.04%	11
Admixed American	0.862%	116
Remaining individualsnot grpmax-eligible	0.684%	146
Middle Eastern	0.529%	189
European (non-Finnish)	0.0358%	2,795
South Asian	0.0187%	5,353
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,550
Finnishnot grpmax-eligible	0.0016%	62,494

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: GSDMD
Protein: p.Ser3=
Coding: c.9G>T
MANE Select: NM_024736
dbSNP: rs7840446
Type: single nucleotide variant
Location: chr8:143559344 (GRCh38)
Gene constraint: LOEUF 1.493 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 11 PDB

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

Similar variants

GSDMD p.Ser3Leu Uncertain significance ★ ⚠ same residue
GSDMD p.Arg249His Benign ★★ same type
GSDMD p.Arg7= Likely benign ★★ same type
GSDMD p.Gln396Arg Benign ★★ same type
GSDMD p.Thr453Ala Benign ★★ same type
GSDMD p.Ala215Thr Uncertain significance ★ ⚠ same type
GSDMD p.Ala244Val Uncertain significance ★ ⚠ same type
GSDMD p.Ala255Thr Uncertain significance ★ ⚠ 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/gsdmd-p-ser3 (accessed [today's date]).

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