Is CCDC59 p.Gln238Pro (c.713A>C) pathogenic?

CCDC59 p.Gln238Pro (c.713A>C) is classified Uncertain significance in CCDC59 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). AlphaMissense: likely pathogenic (0.7124); Very rare (popmax 0.00135%, afr).

How common is CCDC59 p.Gln238Pro (c.713A>C) in the general population?

CCDC59 p.Gln238Pro (c.713A>C) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about CCDC59 p.Gln238Pro (c.713A>C)?

AlphaMissense predicts likely pathogenic (score 0.7124) — an in-silico prediction, not a clinical call.

CCDC59 p.Gln238Pro

c.713A>C · rs781555879 · VCV2311503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7124	likely pathogenic
REVEL	0.502	indeterminate
SaProt	LLR -17.07	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 5,222 bp · p 4.2e-06 · regional, not allelic
Overall
CADD	25.6	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 0.00135% African / African-American · 1/74,008 alleles

Overall 6.91e-05% 1/1,447,858 alleles · very rare

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: CCDC59
Protein: p.Gln238Pro
Coding: c.713A>C
MANE Select: NM_014167
dbSNP: rs781555879
Type: single nucleotide variant
Location: chr12:82353164 (GRCh38)
Gene constraint: LOEUF 1.185 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.09

Full CCDC59 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC59 p.Ala184Val Uncertain significance ★ ⚠ same type
CCDC59 p.Arg109Gly Uncertain significance ★ ⚠ same type
CCDC59 p.Arg11Trp Uncertain significance ★ ⚠ same type
CCDC59 p.Arg50Cys Uncertain significance ★ ⚠ same type
CCDC59 p.Arg5Gly Uncertain significance ★ ⚠ same type
CCDC59 p.Arg6Gly Uncertain significance ★ ⚠ same type
CCDC59 p.Asn216Lys Uncertain significance ★ ⚠ same type
CCDC59 p.Asp131Glu 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/ccdc59-p-gln238pro (accessed [today's date]).

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