Is CHST4 p.Val45Met (c.133G>A) pathogenic?

CHST4 p.Val45Met (c.133G>A) is classified Uncertain significance in CHST4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: ambiguous (0.3486); Ultra-rare (popmax 0.0707%, mid).

How common is CHST4 p.Val45Met (c.133G>A) in the general population?

CHST4 p.Val45Met (c.133G>A) is ultra-rare (popmax 0.0707%, mid) (gnomAD).

What do computational predictors say about CHST4 p.Val45Met (c.133G>A)?

AlphaMissense predicts ambiguous (score 0.3486) — an in-silico prediction, not a clinical call.

CHST4 p.Val45Met

c.133G>A · rs549854802 · VCV2247273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3486 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0707%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3486	ambiguous
REVEL	0.734	pathogenic-leaning
SaProt	LLR -10.33	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 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,157 bp · p 0.075 · regional, not allelic
Overall
CADD	25.3	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 0.0707% Middle Eastern · 4/5,654 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00313% 48/1,531,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0707%	1,413
Admixed American	0.00628%	15,936
African / African-American	0.00553%	18,084
Remaining individualsnot grpmax-eligible	0.0034%	29,437
European (non-Finnish)	0.00289%	34,550
East Asian	0.00227%	44,138
South Asian	0.0013%	76,778

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: CHST4
Protein: p.Val45Met
Coding: c.133G>A
MANE Select: NM_001166395
dbSNP: rs549854802
Type: single nucleotide variant
Location: chr16:71536810 (GRCh38)
Gene constraint: LOEUF 1.836 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 90.66

Full CHST4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST4 p.Ala135Val Uncertain significance ★ ⚠ same type
CHST4 p.Ala167Ser Uncertain significance ★ ⚠ same type
CHST4 p.Ala18Ser Uncertain significance ★ ⚠ same type
CHST4 p.Ala18Thr Uncertain significance ★ ⚠ same type
CHST4 p.Ala333Val Uncertain significance ★ ⚠ same type
CHST4 p.Arg118Gln Uncertain significance ★ ⚠ same type
CHST4 p.Arg130Gln Uncertain significance ★ ⚠ same type
CHST4 p.Arg130Trp 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/chst4-p-val45met (accessed [today's date]).

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