Is CTR9 p.Leu19His (c.56T>A) pathogenic?

CTR9 p.Leu19His (c.56T>A) is classified Likely pathogenic in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-15). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CTR9 p.Leu19His (c.56T>A)?

CTR9 p.Leu19His (c.56T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CTR9 p.Leu19His (c.56T>A) in the general population?

CTR9 p.Leu19His (c.56T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTR9 p.Leu19His (c.56T>A)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

CTR9 p.Leu19His

c.56T>A · rs2539366599 · VCV3078720

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 4% in CTR9
REVEL	0.672	pathogenic-leaning
SaProt	LLR -15.51	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 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.29	constrained · MANE · 1,327 bp · p 6.7e-07 · regional, not allelic
Overall
CADD	29.2	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

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: CTR9
Protein: p.Leu19His
Coding: c.56T>A
MANE Select: NM_014633
dbSNP: rs2539366599
Type: single nucleotide variant
Location: chr11:10752682 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 19: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTR9 p.Ala644Gly Uncertain significance ★★ ⚠ same condition
CTR9 p.Ala897Gly Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1074Trp Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1077Gln Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1163Gly Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg725Gln Uncertain significance ★★ ⚠ same condition
CTR9 p.Asn175Ser Uncertain significance ★★ ⚠ same condition
CTR9 p.Asp1120Asn Uncertain significance ★★ ⚠ same condition

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-leu19his (accessed [today's date]).

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