Is CTR9 p.Asn573Ser (c.1718A>G) pathogenic?

CTR9 p.Asn573Ser (c.1718A>G) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). AlphaMissense: ambiguous (0.3614); Ultra-rare (popmax 0.0165%, mid).

How common is CTR9 p.Asn573Ser (c.1718A>G) in the general population?

CTR9 p.Asn573Ser (c.1718A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CTR9 p.Asn573Ser (c.1718A>G)?

AlphaMissense predicts ambiguous (score 0.3614) — an in-silico prediction, not a clinical call.

CTR9 p.Asn573Ser

c.1718A>G · rs567272474 · VCV1443080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3614 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3614	ambiguous
REVEL	0.255	benign-leaning
SaProt	LLR -5.86	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 5,532 bp · p 3.5e-22 · regional, not allelic
Overall
CADD	23.0	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000929% 15/1,614,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Admixed American	0.00333%	30,006
South Asian	0.00329%	30,362
Remaining individualsnot grpmax-eligible	0.0016%	62,508
African / African-American	0.00133%	75,028
European (non-Finnish)	0.000593%	168,568

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.Asn573Ser
Coding: c.1718A>G
MANE Select: NM_014633
dbSNP: rs567272474
Type: single nucleotide variant
Location: chr11:10767837 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 573: an α-helix

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

Similar variants

CTR9 p.Asn573Ile 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-asn573ser (accessed [today's date]).

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