Is STS p.Arg372Gln (c.1115G>A) pathogenic?

STS p.Arg372Gln (c.1115G>A) is classified Conflicting classifications of pathogenicity in STS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-19). AlphaMissense: ambiguous (0.5096); Ultra-rare (popmax 0.023%, mid); Associated with Inborn genetic diseases.

What condition is associated with STS p.Arg372Gln (c.1115G>A)?

STS p.Arg372Gln (c.1115G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Arg372Gln (c.1115G>A) in the general population?

STS p.Arg372Gln (c.1115G>A) is ultra-rare (popmax 0.023%, mid) (gnomAD).

What do computational predictors say about STS p.Arg372Gln (c.1115G>A)?

AlphaMissense predicts ambiguous (score 0.5096) — an in-silico prediction, not a clinical call.

STS p.Arg372Gln

c.1115G>A · rs753796798 · VCV2356927

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5096 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5096	ambiguous
REVEL	0.891	moderately pathogenic-leaning
SaProt	LLR -11.06	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 6.4, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 25 kb · p 0.038 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R377Q vs ClinVar R372Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.023% Middle Eastern · 1/4,354 alleles

Filtering AF 0.00508% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00465%

Overall 0.00574% 63/1,097,979 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,354
Ashkenazi Jewishnot grpmax-eligible	0.00908%	11,018
European (non-Finnish)	0.00648%	15,436
Finnishnot grpmax-eligible	0.00213%	46,867
Remaining individualsnot grpmax-eligible	0.0021%	47,631

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: STS
Protein: p.Arg372Gln
Coding: c.1115G>A
MANE Select: NM_001320752
dbSNP: rs753796798
Type: single nucleotide variant
Location: chrX:7325372 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 372: a UniProt-annotated variant site (in ixl; loss of steryl-sulfatase activity); a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STS p.Arg372Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
STS p.Arg381Ser Uncertain significance ★★ ⚠ same condition
STS p.Asp397Asn Uncertain significance ★★ ⚠ same condition
STS p.Arg578His Benign/Likely benign ★★ same condition
STS c.943+5G>A Conflicting classifications of pathogenicity ★ same condition
STS p.Ala295Val Uncertain significance ★ ⚠ same condition
STS p.Ala529Val Uncertain significance ★ ⚠ same condition
STS p.Arg179Ser Uncertain significance ★ ⚠ 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/sts-p-arg372gln (accessed [today's date]).

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