Is CTH p.Arg62Pro (c.185G>C) pathogenic?

CTH p.Arg62Pro (c.185G>C) is classified Uncertain significance in CTH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). AlphaMissense: likely pathogenic (0.989); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTH p.Arg62Pro (c.185G>C)?

CTH p.Arg62Pro (c.185G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CTH p.Arg62Pro (c.185G>C) in the general population?

CTH p.Arg62Pro (c.185G>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CTH p.Arg62Pro (c.185G>C)?

AlphaMissense predicts likely pathogenic (score 0.989) — an in-silico prediction, not a clinical call.

CTH p.Arg62Pro

c.185G>C · VCV3498164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.989	likely pathogenic · top 1% in CTH
REVEL	0.952	strongly pathogenic-leaning
SaProt	LLR -15.33	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 9.8	GERP 2, phastCons 1
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00134% African / African-American · 1/74,784 alleles

Filtering AF 0.000545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000808% 13/1,608,198 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,784
European (non-Finnish)	0.00102%	97,894

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: CTH
Protein: p.Arg62Pro
Coding: c.185G>C
MANE Select: NM_014312 · reported on NM_001902
Type: single nucleotide variant
Location: chr1:70415972 (GRCh38)
Structure: AlphaFold pLDDT 80.30
Residue 62: a disulfide bond; the ig-like v-type domain

Full CTH 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

CTH p.Asp181Asn Uncertain significance ★★ ⚠ same condition
CTH p.Thr158Ile Uncertain significance ★★ ⚠ same condition
CTH p.Ala103Ser Uncertain significance ★ ⚠ same condition
CTH p.Ala146Pro Uncertain significance ★ ⚠ same condition
CTH p.Ala245Thr Uncertain significance ★ ⚠ same condition
CTH p.Ala51Thr Uncertain significance ★ ⚠ same condition
CTH p.Ala6Thr Uncertain significance ★ ⚠ same condition
CTH p.Asn234Asp 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/cth-p-arg62pro (accessed [today's date]).

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