Is CHST8 p.Phe272Ser (c.815T>C) pathogenic?

CHST8 p.Phe272Ser (c.815T>C) is classified Uncertain significance in CHST8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely pathogenic (0.9986); Ultra-rare (popmax 0.025%, amr).

How common is CHST8 p.Phe272Ser (c.815T>C) in the general population?

CHST8 p.Phe272Ser (c.815T>C) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about CHST8 p.Phe272Ser (c.815T>C)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

CHST8 p.Phe272Ser

c.815T>C · rs776947439 · VCV2405144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic · top 1% in CHST8
REVEL	0.88	moderately pathogenic-leaning
SaProt	LLR -16.36	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 84 kb · p 0.3 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.025% Admixed American · 15/60,006 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0013% 21/1,613,896 alleles · ultra-rare exomes 10/1,461,726 · genomes 11/152,170 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	4,000
Remaining individualsnot grpmax-eligible	0.0048%	20,829
South Asian	0.0022%	45,541
African / African-American	0.00133%	74,936

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: CHST8
Protein: p.Phe272Ser
Coding: c.815T>C
MANE Select: NM_001127895
dbSNP: rs776947439
Type: single nucleotide variant
Location: chr19:33772603 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.90

Full CHST8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHST8 p.Val186Ala Uncertain significance ★★ ⚠ same type
CHST8 c.168+64G>A Benign ★★ same type
CHST8 c.-86-36C>T Benign ★★ same type
CHST8 p.Arg9= Benign ★★ same type
CHST8 p.Leu288= Benign ★★ same type
CHST8 p.Ala23Gly Uncertain significance ★ ⚠ same type
CHST8 p.Ala293Pro Uncertain significance ★ ⚠ same type
CHST8 p.Ala293Ser 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/chst8-p-phe272ser (accessed [today's date]).

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