Is CTR9 p.Ala483Glu (c.1448C>A) pathogenic?

CTR9 p.Ala483Glu (c.1448C>A) is classified Likely benign in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-04). AlphaMissense: likely benign (0.302); Rare (popmax 0.24%, sas).

How common is CTR9 p.Ala483Glu (c.1448C>A) in the general population?

CTR9 p.Ala483Glu (c.1448C>A) is rare (popmax 0.24%, sas) (gnomAD).

What do computational predictors say about CTR9 p.Ala483Glu (c.1448C>A)?

AlphaMissense predicts likely benign (score 0.302) — an in-silico prediction, not a clinical call.

CTR9 p.Ala483Glu

c.1448C>A · rs536618493 · VCV2181503

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.302 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.24%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.302	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -5.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this 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	20.9	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 0.24% South Asian · 218/90,932 alleles

Filtering AF 0.214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.0141% 227/1,612,052 alleles · rare exomes 219/1,459,790 · genomes 8/152,262 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.24%	417
Remaining individualsnot grpmax-eligible	0.0128%	7,801
Admixed American	0.00167%	59,930

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.Ala483Glu
Coding: c.1448C>A
MANE Select: NM_014633
dbSNP: rs536618493
Type: single nucleotide variant
Location: chr11:10764582 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 483: an α-helix

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

Similar variants

CTR9 p.Ala483Gly Uncertain significance ★ ⚠ 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-ala483glu (accessed [today's date]).

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