Is CTR9 p.Asp108Val (c.323A>T) pathogenic?

CTR9 p.Asp108Val (c.323A>T) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). AlphaMissense: ambiguous (0.4792); Very rare (popmax 8.48e-05%, nfe).

How common is CTR9 p.Asp108Val (c.323A>T) in the general population?

CTR9 p.Asp108Val (c.323A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CTR9 p.Asp108Val (c.323A>T)?

AlphaMissense predicts ambiguous (score 0.4792) — an in-silico prediction, not a clinical call.

CTR9 p.Asp108Val

c.323A>T · VCV4686494

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4792	ambiguous
REVEL	0.446	indeterminate
SaProt	LLR -8.60	tolerated
Splicing
SpliceAI	Δ0.62	donor gain · deltas
Pangolin	Δ0.50	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 2,447 bp · p 0.00011 · regional, not allelic
Overall
CADD	32.0	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 8.48e-05% European (non-Finnish) · 1/1,179,754 alleles

Overall 6.84e-05% 1/1,461,496 alleles · very rare

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.Asp108Val
Coding: c.323A>T
MANE Select: NM_014633
Type: single nucleotide variant
Location: chr11:10755136 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 108: an α-helix

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

Similar variants

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
CTR9 c.593-8T>A 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-asp108val (accessed [today's date]).

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