Is CHST5 p.Val229Met (c.685G>A) pathogenic?

CHST5 p.Val229Met (c.685G>A) is classified Uncertain significance in CHST5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: ambiguous (0.4637); Rare (popmax 0.113%, nfe).

How common is CHST5 p.Val229Met (c.685G>A) in the general population?

CHST5 p.Val229Met (c.685G>A) is rare (popmax 0.113%, nfe) (gnomAD).

What do computational predictors say about CHST5 p.Val229Met (c.685G>A)?

AlphaMissense predicts ambiguous (score 0.4637) — an in-silico prediction, not a clinical call.

CHST5 p.Val229Met

c.685G>A · rs147923696 · VCV2249525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4637 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.113%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4637	ambiguous
REVEL	0.371	indeterminate
SaProt	LLR -9.16	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.82, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,232 bp · p 0.16 · regional, not allelic
Overall
CADD	27.1	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 0.113% European (non-Finnish) · 1,329/1,178,838 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.091% 1,466/1,610,994 alleles · rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.127%	790
European (non-Finnish)grpmax	0.113%	887
Admixed American	0.0384%	2,605
Ashkenazi Jewishnot grpmax-eligible	0.0373%	2,682
African / African-American	0.0227%	4,410
South Asian	0.0044%	22,744
Finnishnot grpmax-eligible	0.00319%	31,331
East Asian	0.00223%	44,796

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val229Met
Coding: c.685G>A
MANE Select: NM_024533
dbSNP: rs147923696
Type: single nucleotide variant
Location: chr16:75529700 (GRCh38)
Gene constraint: LOEUF 1.549 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 88.60
Residue 229: a binding site

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-val229met (accessed [today's date]).

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