Is CHST5 p.Ser83Asn (c.248G>A) pathogenic?

CHST5 p.Ser83Asn (c.248G>A) is classified Uncertain significance in CHST5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: ambiguous (0.365); Ultra-rare (popmax 0.0253%, afr).

How common is CHST5 p.Ser83Asn (c.248G>A) in the general population?

CHST5 p.Ser83Asn (c.248G>A) is ultra-rare (popmax 0.0253%, afr) (gnomAD).

What do computational predictors say about CHST5 p.Ser83Asn (c.248G>A)?

AlphaMissense predicts ambiguous (score 0.365) — an in-silico prediction, not a clinical call.

CHST5 p.Ser83Asn

c.248G>A · VCV3267240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.365 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, afr)

Computational evidence

Protein change
AlphaMissense	0.365	ambiguous
REVEL	0.321	indeterminate
SaProt	LLR -1.96	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.86, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,232 bp · p 0.16 · regional, not allelic
Overall
CADD	20.9	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 0.0253% African / African-American · 19/75,056 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00167% 27/1,613,570 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0253%	3,950
European (non-Finnish)	0.000678%	147,500

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: CHST5
Protein: p.Ser83Asn
Coding: c.248G>A
MANE Select: NM_024533
Type: single nucleotide variant
Location: chr16:75530137 (GRCh38)
Gene constraint: LOEUF 1.549 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 88.60

Full CHST5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST5 p.Ala311Thr Benign ★★ same type
CHST5 p.Arg6Trp Benign ★★ ⚠ same type
CHST5 p.Glu322Gln Benign ★★ same type
CHST5 p.Ala11Val Uncertain significance ★ ⚠ same type
CHST5 p.Ala150Glu Uncertain significance ★ ⚠ same type
CHST5 p.Ala159Thr Uncertain significance ★ ⚠ same type
CHST5 p.Ala214Thr Uncertain significance ★ ⚠ same type
CHST5 p.Ala275Ser 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/chst5-p-ser83asn (accessed [today's date]).

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