Is CTR9 p.Glu59Asp (c.177G>T) pathogenic?

CTR9 p.Glu59Asp (c.177G>T) is classified Uncertain significance in CTR9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely benign (0.041); Absent from gnomAD v4.1; Associated with CTR9-related motor delay and macrocephaly.

What condition is associated with CTR9 p.Glu59Asp (c.177G>T)?

CTR9 p.Glu59Asp (c.177G>T) is associated with CTR9-related motor delay and macrocephaly (ClinVar).

How common is CTR9 p.Glu59Asp (c.177G>T) in the general population?

CTR9 p.Glu59Asp (c.177G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTR9 p.Glu59Asp (c.177G>T)?

AlphaMissense predicts likely benign (score 0.041) — an in-silico prediction, not a clinical call.

CTR9 p.Glu59Asp

c.177G>T · VCV4293234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.041 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CTR9-related motor delay and macrocephaly

Computational evidence

Protein change
AlphaMissense	0.041	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -5.70	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 1.4	GERP -2.9, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 2,447 bp · p 0.00011 · regional, not allelic
Overall
CADD	13.17	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Glu59Asp
Coding: c.177G>T
MANE Select: NM_014633
Type: single nucleotide variant
Location: chr11:10754990 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.62 · 21 PDB
Residue 59: an α-helix

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

Disease context

CTR9-related motor delay and macrocephaly

Similar variants

CTR9 c.1960+3G>A Uncertain significance ★★ same condition
CTR9 c.45+5G>T Uncertain significance ★★ same condition
CTR9 p.Ala370Thr Uncertain significance ★★ ⚠ same condition
CTR9 p.Ala567Ser Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1095Lys Uncertain significance ★★ ⚠ same condition
CTR9 p.Arg1122His Uncertain significance ★★ ⚠ same condition
CTR9 p.Lys282Arg Uncertain significance ★★ ⚠ same condition
CTR9 p.Tyr385Cys 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-glu59asp (accessed [today's date]).

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