Is IGSF1 p.Ser464= (c.1392A>C) pathogenic?

IGSF1 p.Ser464= (c.1392A>C) is classified Likely benign in IGSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-19). Absent from gnomAD v4.1.

How common is IGSF1 p.Ser464= (c.1392A>C) in the general population?

IGSF1 p.Ser464= (c.1392A>C) is absent from gnomAD v4.1 (gnomAD).

IGSF1 p.Ser464=

c.1392A>C · VCV4952859

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.85	GERP -1.7
Overall
CADD	3.231	PHRED · no single calibrated threshold — expert panels disagree

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: IGSF1
Protein: p.Ser464=
Coding: c.1392A>C
MANE Select: NM_001555
Type: single nucleotide variant
Location: chrX:131281799 (GRCh38)
Structure: AlphaFold pLDDT 73.64
Residue 464: the ig-like c2-type 5 domain

Full IGSF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IGSF1 p.Ser464Pro Uncertain significance ★ ⚠ same residue
IGSF1 p.Arg1184Ter Pathogenic ★★ same type
IGSF1 p.Asp853Gly Uncertain significance ★★ ⚠ same type
IGSF1 p.Ile1221Thr Uncertain significance ★★ ⚠ same type
IGSF1 p.Thr1302Ile Uncertain significance ★★ ⚠ same type
IGSF1 p.Thr1316Ile Uncertain significance ★★ ⚠ same type
IGSF1 c.2041+24G>A Benign ★★ same type
IGSF1 c.2042-70G>C 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/igsf1-p-ser464 (accessed [today's date]).

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