Is CHST5 p.Ser29Arg (c.85A>C) pathogenic?

CHST5 p.Ser29Arg (c.85A>C) is classified Uncertain significance in CHST5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.2433); Ultra-rare (popmax 0.0165%, mid).

How common is CHST5 p.Ser29Arg (c.85A>C) in the general population?

CHST5 p.Ser29Arg (c.85A>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CHST5 p.Ser29Arg (c.85A>C)?

AlphaMissense predicts likely benign (score 0.2433) — an in-silico prediction, not a clinical call.

CHST5 p.Ser29Arg

c.85A>C · VCV4002778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2433 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2433	likely benign
REVEL	0.508	indeterminate
SaProt	LLR -4.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.059	GERP 0.57, phastCons 0.13
Regional constraint	o/e 1.06	unconstrained · MANE · 1,232 bp · p 0.16 · regional, not allelic
Overall
CADD	9.281	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,054 alleles

Filtering AF 0.00411% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.0046% 74/1,610,400 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,054
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,837
South Asian	0.00663%	15,094
European (non-Finnish)	0.00517%	19,324
Finnishnot grpmax-eligible	0.00318%	31,472
Remaining individualsnot grpmax-eligible	0.00161%	62,288

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.Ser29Arg
Coding: c.85A>C
MANE Select: NM_024533
Type: single nucleotide variant
Location: chr16:75530300 (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.Ser29Asn Uncertain significance ★ ⚠ same residue
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

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-ser29arg (accessed [today's date]).

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