Is CCDC61 p.Pro290Leu (c.869C>T) pathogenic?

CCDC61 p.Pro290Leu (c.869C>T) is classified Likely benign in CCDC61 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-27). AlphaMissense: likely benign (0.0696); Rare (popmax 0.374%, nfe).

How common is CCDC61 p.Pro290Leu (c.869C>T) in the general population?

CCDC61 p.Pro290Leu (c.869C>T) is rare (popmax 0.374%, nfe) (gnomAD).

What do computational predictors say about CCDC61 p.Pro290Leu (c.869C>T)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

CCDC61 p.Pro290Leu

c.869C>T · rs748603545 · VCV781453

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.374%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.62	GERP -2
Regional constraint	o/e 0.89	unconstrained · MANE · 15 kb · p 0.0029 · regional, not allelic
Overall
CADD	7.35	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 0.374% European (non-Finnish) · 3,707/990,370 alleles

Filtering AF 0.364% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.36%

Overall 0.314% 3,881/1,234,706 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.374%	267
Remaining individualsnot grpmax-eligible	0.189%	528
Finnishnot grpmax-eligible	0.116%	865
African / African-American	0.0621%	1,611
Middle Eastern	0.0311%	3,216
Admixed American	0.0295%	3,384
Ashkenazi Jewishnot grpmax-eligible	0.00561%	17,828
South Asian	0.00405%	24,674

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: CCDC61
Protein: p.Pro290Leu
Coding: c.869C>T
MANE Select: NM_001267723
dbSNP: rs748603545
Type: single nucleotide variant
Location: chr19:46016077 (GRCh38)
Gene constraint: LOEUF 1.318 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.97 · 1 PDB
Residue 290: the 'disordered' region

Full CCDC61 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC61 p.Ser512Pro 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/ccdc61-p-pro290leu (accessed [today's date]).

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