Is CCDC116 p.Leu286Phe (c.856C>T) pathogenic?

CCDC116 p.Leu286Phe (c.856C>T) is classified Likely benign in CCDC116 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.0978); Very rare (popmax 0.00833%, amr).

How common is CCDC116 p.Leu286Phe (c.856C>T) in the general population?

CCDC116 p.Leu286Phe (c.856C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CCDC116 p.Leu286Phe (c.856C>T)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

CCDC116 p.Leu286Phe

c.856C>T · VCV4220338

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.27	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 -0.07	GERP -3.4
Regional constraint	o/e 0.98	unconstrained · MANE · 3,885 bp · p 0.65 · regional, not allelic
Overall
CADD	1.338	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 0.00833% Admixed American · 5/60,024 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000342% 5/1,461,666 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: CCDC116
Protein: p.Leu286Phe
Coding: c.856C>T
MANE Select: NM_152612
Type: single nucleotide variant
Location: chr22:21634919 (GRCh38)
Gene constraint: LOEUF 1.158 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.59

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

Similar variants

CCDC116 p.Leu286= Likely benign ★ same residue
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.Pro293Leu Benign ★★ same type
CCDC116 p.Thr569= Benign ★★ same type
CCDC116 p.Val252Met Benign ★★ ⚠ 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-leu286phe (accessed [today's date]).

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