Is CHST7 p.Arg354Ser (c.1060C>A) pathogenic?

CHST7 p.Arg354Ser (c.1060C>A) is classified Uncertain significance in CHST7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-27). AlphaMissense: ambiguous (0.5011); Ultra-rare (popmax 0.0484%, mid).

How common is CHST7 p.Arg354Ser (c.1060C>A) in the general population?

CHST7 p.Arg354Ser (c.1060C>A) is ultra-rare (popmax 0.0484%, mid) (gnomAD).

What do computational predictors say about CHST7 p.Arg354Ser (c.1060C>A)?

AlphaMissense predicts ambiguous (score 0.5011) — an in-silico prediction, not a clinical call.

CHST7 p.Arg354Ser

c.1060C>A · rs2519300759 · VCV2530041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5011 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0484%, mid)

Computational evidence

Protein change
AlphaMissense	0.5011	ambiguous
REVEL	0.368	indeterminate
SaProt	LLR -8.53	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -3.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 373 bp · p 0.67 · regional, not allelic
Overall
CADD	22.2	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

Grpmax group 0.0484% Middle Eastern · 2/4,134 alleles

Filtering AF 0.00852% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00355%

Overall 0.000291% 3/1,031,497 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0484%	2,067
European (non-Finnish)	0.000114%	873,446

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: CHST7
Protein: p.Arg354Ser
Coding: c.1060C>A
MANE Select: NM_019886
dbSNP: rs2519300759
Type: single nucleotide variant
Location: chrX:46574991 (GRCh38)
Structure: AlphaFold pLDDT 80.60

Full CHST7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST7 p.Asp266= Benign ★★ same type
CHST7 p.Ala172Thr Uncertain significance ★ ⚠ same type
CHST7 p.Ala337Thr Uncertain significance ★ ⚠ same type
CHST7 p.Ala413Ser Uncertain significance ★ ⚠ same type
CHST7 p.Ala413Thr Uncertain significance ★ ⚠ same type
CHST7 p.Ala453Val Uncertain significance ★ ⚠ same type
CHST7 p.Arg323Cys Uncertain significance ★ ⚠ same type
CHST7 p.Arg367Gln 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/chst7-p-arg354ser (accessed [today's date]).

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