Is CHST5 p.Phe27Ile (c.79T>A) pathogenic?

CHST5 p.Phe27Ile (c.79T>A) is classified Uncertain significance in CHST5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: likely benign (0.0653); Very rare (popmax 6.86e-05%).

How common is CHST5 p.Phe27Ile (c.79T>A) in the general population?

CHST5 p.Phe27Ile (c.79T>A) is very rare (popmax 6.86e-05%) (gnomAD).

What do computational predictors say about CHST5 p.Phe27Ile (c.79T>A)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

CHST5 p.Phe27Ile

c.79T>A · rs778989892 · VCV2538467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.86e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.394	indeterminate
SaProt	LLR -7.15	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 -3.1	GERP -3.3
Regional constraint	o/e 1.06	unconstrained · MANE · 1,232 bp · p 0.16 · regional, not allelic
Overall
CADD	0.009	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 6.86e-05%

Overall 6.86e-05% 1/1,457,192 alleles · very rare

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.Phe27Ile
Coding: c.79T>A
MANE Select: NM_024533
dbSNP: rs778989892
Type: single nucleotide variant
Location: chr16:75530306 (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-phe27ile (accessed [today's date]).

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