Is CTR9 p.Arg985His (c.2954G>A) pathogenic?

CTR9 p.Arg985His (c.2954G>A) is classified Conflicting classifications of pathogenicity in CTR9 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-05). AlphaMissense: likely benign (0.1848); Ultra-rare (popmax 0.0201%, eas).

How common is CTR9 p.Arg985His (c.2954G>A) in the general population?

CTR9 p.Arg985His (c.2954G>A) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about CTR9 p.Arg985His (c.2954G>A)?

AlphaMissense predicts likely benign (score 0.1848) — an in-silico prediction, not a clinical call.

CTR9 p.Arg985His

c.2954G>A · rs372648972 · VCV1052928

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1848 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1848	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -9.62	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,491 bp · p 0.47 · regional, not allelic
Overall
CADD	27.0	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 0.0201% East Asian · 9/44,886 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00297% 48/1,613,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,987
South Asian	0.00329%	30,355
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00263%	38,063
Admixed American	0.00167%	59,974
Finnishnot grpmax-eligible	0.00156%	63,994
African / African-American	0.00134%	74,902

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.Arg985His
Coding: c.2954G>A
MANE Select: NM_014633
dbSNP: rs372648972
Type: single nucleotide variant
Location: chr11:10775275 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 985: the 'disordered' region

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

Similar variants

CTR9 p.Arg985Cys Uncertain significance ★ ⚠ same residue
CTR9 p.Arg985= 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

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-arg985his (accessed [today's date]).

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