Is CTR9 p.Ala476Val (c.1427C>T) pathogenic?

CTR9 p.Ala476Val (c.1427C>T) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). AlphaMissense: ambiguous (0.4504); Ultra-rare (popmax 0.0171%, amr).

How common is CTR9 p.Ala476Val (c.1427C>T) in the general population?

CTR9 p.Ala476Val (c.1427C>T) is ultra-rare (popmax 0.0171%, amr) (gnomAD).

What do computational predictors say about CTR9 p.Ala476Val (c.1427C>T)?

AlphaMissense predicts ambiguous (score 0.4504) — an in-silico prediction, not a clinical call.

CTR9 p.Ala476Val

c.1427C>T · rs760130762 · VCV1381912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4504 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, amr)

Computational evidence

Protein change
AlphaMissense	0.4504	ambiguous
REVEL	0.498	indeterminate
SaProt	LLR -8.30	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 1,051 bp · p 1.2e-12 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0171% Admixed American · 10/58,392 alleles

Filtering AF 0.00923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00698%

Overall 0.00119% 19/1,602,922 alleles · ultra-rare exomes 19/1,450,762 · genomes 0/152,160 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0171%	5,839
South Asian	0.00556%	17,997
European (non-Finnish)	0.000341%	293,354

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: CTR9
Protein: p.Ala476Val
Coding: c.1427C>T
MANE Select: NM_014633
dbSNP: rs760130762
Type: single nucleotide variant
Location: chr11:10764561 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 476: an α-helix

Full CTR9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTR9 p.Ala476= Likely benign ★ same residue
CTR9 p.Asn455Ser Likely pathogenic ★★ same type
CTR9 p.Ile17Thr Pathogenic/Likely pathogenic ★★ same type
CTR9 p.Pro25Arg Pathogenic/Likely pathogenic ★★ same type
CTR9 c.1960+3G>A Uncertain significance ★★ same type
CTR9 c.2109+4A>G Uncertain significance ★★ same type
CTR9 c.2445-3T>C Uncertain significance ★★ same type
CTR9 c.45+5G>T 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/ctr9-p-ala476val (accessed [today's date]).

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