Is CRAT p.Phe414Ser (c.1241T>C) pathogenic?

CRAT p.Phe414Ser (c.1241T>C) is classified Uncertain significance in CRAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely pathogenic (0.9771); Absent from gnomAD v4.1.

How common is CRAT p.Phe414Ser (c.1241T>C) in the general population?

CRAT p.Phe414Ser (c.1241T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRAT p.Phe414Ser (c.1241T>C)?

AlphaMissense predicts likely pathogenic (score 0.9771) — an in-silico prediction, not a clinical call.

CRAT p.Phe414Ser

c.1241T>C · VCV4742075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9771 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9771	likely pathogenic · top 8% in CRAT
REVEL	0.987	strongly pathogenic-leaning
SaProt	LLR -13.61	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 0.00046 · regional, not allelic
Overall
CADD	29.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRAT
Protein: p.Phe414Ser
Coding: c.1241T>C
MANE Select: NM_000755
Type: single nucleotide variant
Location: chr9:129098336 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.75 · 3 PDB
Residue 414: 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-phe414ser (accessed [today's date]).

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