Is CRAT p.Phe28= (c.84C>T) pathogenic?

CRAT p.Phe28= (c.84C>T) is classified Likely benign in CRAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-18). Very rare (popmax 0.00243%, nfe).

How common is CRAT p.Phe28= (c.84C>T) in the general population?

CRAT p.Phe28= (c.84C>T) is very rare (popmax 0.00243%, nfe) (gnomAD).

CRAT p.Phe28=

c.84C>T · rs1430281444 · VCV3005654

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00243%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -0.43, phastCons 1
Overall
CADD	8.686	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00243% European (non-Finnish) · 28/1,153,080 alleles

Filtering AF 0.00168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00145%

Overall 0.00187% 29/1,553,640 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00243%	41,181
Finnishnot grpmax-eligible	0.0019%	52,714

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: CRAT
Protein: p.Phe28=
Coding: c.84C>T
MANE Select: NM_000755
dbSNP: rs1430281444
Type: single nucleotide variant
Location: chr9:129108021 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.75 · 3 PDB

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

Similar variants

CRAT p.Phe28Leu Uncertain significance ★ ⚠ same residue
CRAT p.Ala260Pro Uncertain significance ★★ ⚠ same type
CRAT p.Ala262Thr Uncertain significance ★★ ⚠ same type
CRAT p.Ala544Thr Uncertain significance ★★ ⚠ same type
CRAT p.Ala546Thr Uncertain significance ★★ ⚠ same type
CRAT p.Ala596Thr Uncertain significance ★★ ⚠ same type
CRAT p.Ala596Val Uncertain significance ★★ ⚠ same type
CRAT p.Ala600Thr 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/crat-p-phe28 (accessed [today's date]).

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