Is CCDC116 p.Pro293Leu (c.878C>T) pathogenic?

CCDC116 p.Pro293Leu (c.878C>T) is classified Benign in CCDC116 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-27). AlphaMissense: likely benign (0.125); Common (popmax 6.73%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CCDC116 p.Pro293Leu (c.878C>T)?

AlphaMissense predicts likely benign (score 0.125) — an in-silico prediction, not a clinical call.

CCDC116 p.Pro293Leu

Q: How common is CCDC116 p.Pro293Leu (c.878C>T) in the general population?

CCDC116 p.Pro293Leu (c.878C>T) is common (popmax 6.73%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.878C>T · rs41279987 · VCV781611

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.125 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.73%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.125	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.32	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 0.64, phastCons 0.001
Regional constraint	o/e 0.98	unconstrained · MANE · 3,885 bp · p 0.65 · regional, not allelic
Overall
CADD	16.39	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 6.73% African / African-American · 5,052/75,024 alleles

Filtering AF 6.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.52%

Overall 0.382% 6,172/1,613,724 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.73%	15
Admixed American	0.715%	140
Middle Eastern	0.627%	160
Remaining individualsnot grpmax-eligible	0.563%	178
Finnishnot grpmax-eligible	0.0299%	3,349
European (non-Finnish)	0.0229%	4,370
South Asian	0.0132%	7,591

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: CCDC116
Protein: p.Pro293Leu
Coding: c.878C>T
MANE Select: NM_152612
dbSNP: rs41279987
Type: single nucleotide variant
Location: chr22:21634941 (GRCh38)
Gene constraint: LOEUF 1.158 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.59
Residue 293: a UniProt-annotated variant site (in)

Full CCDC116 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC116 c.73-8C>T Benign ★★ same type
CCDC116 p.Arg174= Benign ★★ same type
CCDC116 p.Asn302= Benign ★★ same type
CCDC116 p.Lys412Arg Benign ★★ same type
CCDC116 p.Thr569= Benign ★★ same type
CCDC116 p.Val252Met Benign ★★ ⚠ same type
CCDC116 p.Ala12Asp Uncertain significance ★ ⚠ same type
CCDC116 p.Ala255Thr 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/ccdc116-p-pro293leu (accessed [today's date]).

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