Is GSDMD p.Phe240Ser (c.719T>C) pathogenic?

GSDMD p.Phe240Ser (c.719T>C) is classified Uncertain significance in GSDMD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-30). AlphaMissense: likely pathogenic (0.9089); Absent from gnomAD v4.1.

How common is GSDMD p.Phe240Ser (c.719T>C) in the general population?

GSDMD p.Phe240Ser (c.719T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GSDMD p.Phe240Ser (c.719T>C)?

AlphaMissense predicts likely pathogenic (score 0.9089) — an in-silico prediction, not a clinical call.

GSDMD p.Phe240Ser

c.719T>C · VCV3523012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9089 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9089	likely pathogenic · top 1% in GSDMD
REVEL	0.239	benign-leaning
SaProt	LLR -11.54	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 3,565 bp · p 0.69 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GSDMD
Protein: p.Phe240Ser
Coding: c.719T>C
MANE Select: NM_024736
Type: single nucleotide variant
Location: chr8:143561406 (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.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
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-phe240ser (accessed [today's date]).

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