Is GSDMD p.Pro365= (c.1095G>A) pathogenic?

GSDMD p.Pro365= (c.1095G>A) is classified Likely benign in GSDMD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). Rare (popmax 0.102%, mid).

How common is GSDMD p.Pro365= (c.1095G>A) in the general population?

GSDMD p.Pro365= (c.1095G>A) is rare (popmax 0.102%, mid) (gnomAD).

GSDMD p.Pro365=

c.1095G>A · rs373406712 · VCV2658900

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.102%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.6	GERP -0.75
Overall
CADD	6.994	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% Middle Eastern · 6/5,910 alleles

Filtering AF 0.0737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0678%

Overall 0.0243% 376/1,544,546 alleles · rare exomes 345/1,394,484 · genomes 31/150,062 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.448%	223
Middle Easterngrpmax	0.102%	985
South Asian	0.0901%	1,110
Remaining individualsnot grpmax-eligible	0.0652%	1,534
Admixed American	0.0118%	8,509
European (non-Finnish)	0.0103%	9,700
African / African-American	0.00411%	24,349
Finnishnot grpmax-eligible	0.00181%	55,360

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: GSDMD
Protein: p.Pro365=
Coding: c.1095G>A
MANE Select: NM_024736
dbSNP: rs373406712
Type: single nucleotide variant
Location: chr8:143562307 (GRCh38)
Gene constraint: LOEUF 1.493 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 11 PDB
Residue 365: an α-helix

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

Similar variants

GSDMD p.Pro365Leu 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.Ser3= Benign ★★ same type
GSDMD p.Thr453Ala Benign ★★ same type
GSDMD p.Ala215Thr Uncertain significance ★ ⚠ same type
GSDMD p.Ala244Val 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-pro365 (accessed [today's date]).

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