Is CRAT p.Thr285= (c.855C>T) pathogenic?

CRAT p.Thr285= (c.855C>T) is classified Likely benign in CRAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). Very rare (popmax 0.004%, afr).

How common is CRAT p.Thr285= (c.855C>T) in the general population?

CRAT p.Thr285= (c.855C>T) is very rare (popmax 0.004%, afr) (gnomAD).

CRAT p.Thr285=

c.855C>T · rs745764628 · VCV1912208

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -8.1	GERP -4
Overall
CADD	3.403	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,944 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00496% 80/1,613,944 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.075%	1,333
Remaining individualsnot grpmax-eligible	0.0064%	15,620
African / African-Americangrpmax	0.004%	24,981
European (non-Finnish)	0.00212%	47,199

Finnish 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: CRAT
Protein: p.Thr285=
Coding: c.855C>T
MANE Select: NM_000755
dbSNP: rs745764628
Type: single nucleotide variant
Location: chr9:129100640 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.75 · 3 PDB
Residue 285: a β-strand

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

Similar variants

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
CRAT p.Ala604Val 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-thr285 (accessed [today's date]).

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