IGSF1 p.Val1193=

Q: Is IGSF1 p.Val1193= (c.3579C>T) pathogenic?

IGSF1 p.Val1193= (c.3579C>T) is classified Benign in IGSF1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Common (popmax 81.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with X-linked central congenital hypothyroidism with late-onset testicular enlargement.

Q: What condition is associated with IGSF1 p.Val1193= (c.3579C>T)?

IGSF1 p.Val1193= (c.3579C>T) is associated with X-linked central congenital hypothyroidism with late-onset testicular enlargement (ClinVar).

Q: How common is IGSF1 p.Val1193= (c.3579C>T) in the general population?

IGSF1 p.Val1193= (c.3579C>T) is common (popmax 81.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is X-linked central congenital hypothyroidism with late-onset testicular enlargement inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.3579C>T · rs6529473 · VCV257592

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 81.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

X-linked central congenital hypothyroidism with late-onset testicular enlargement

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.31	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.3	GERP -3.6, phastCons 1
Overall
CADD	13.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 81.7% East Asian · 27,497/33,676 alleles

Filtering AF 80.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 80.5%

Overall 26.7% 322,261/1,208,393 alleles · common exomes 289,224/1,097,802 · genomes 33,037/110,591 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	81.7%	1
Admixed American	49.4%	2
South Asian	42.2%	2
African / African-American	35%	3
Remaining individualsnot grpmax-eligible	29.7%	3
Ashkenazi Jewishnot grpmax-eligible	25.7%	4
Finnishnot grpmax-eligible	23.9%	4
Middle Eastern	23.4%	4
European (non-Finnish)	22%	5
Amishnot grpmax-eligible	13.7%	7

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: IGSF1
Protein: p.Val1193=
Coding: c.3579C>T
MANE Select: NM_001555
dbSNP: rs6529473
Type: single nucleotide variant
Location: chrX:131274771 (GRCh38)
Structure: AlphaFold pLDDT 73.64
Residue 1193: the ig-like c2-type 12 domain

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

Disease context

X-linked central congenital hypothyroidism with late-onset testicular enlargement — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked central congenital hypothyroidism with late-onset testicular enlargement (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

IGSF1 p.Arg1184Ter Pathogenic ★★ same condition
IGSF1 c.2041+24G>A Benign ★★ same condition
IGSF1 p.Asn381His Benign/Likely benign ★★ same condition
IGSF1 p.Glu449= Benign ★★ same condition
IGSF1 p.Pro38= Benign ★★ same condition
IGSF1 p.Ser31= Benign ★★ same condition
IGSF1 p.Tyr852= Benign ★★ same condition
IGSF1 p.Val316= Benign ★★ same condition

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-val1193 (accessed [today's date]).

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