Is CCDC116 p.Lys412Arg (c.1235A>G) pathogenic?

CCDC116 p.Lys412Arg (c.1235A>G) is classified Benign in CCDC116 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-18). AlphaMissense: likely benign (0.1154); Low-frequency (popmax 2.18%, afr).

How common is CCDC116 p.Lys412Arg (c.1235A>G) in the general population?

CCDC116 p.Lys412Arg (c.1235A>G) is low-frequency (popmax 2.18%, afr) (gnomAD).

What do computational predictors say about CCDC116 p.Lys412Arg (c.1235A>G)?

AlphaMissense predicts likely benign (score 0.1154) — an in-silico prediction, not a clinical call.

CCDC116 p.Lys412Arg

c.1235A>G · rs148692511 · VCV777668

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1154 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.18%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1154	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.00	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 3.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,885 bp · p 0.65 · regional, not allelic
Overall
CADD	21.8	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 2.18% African / African-American · 1,633/75,020 alleles

Filtering AF 2.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.05%

Overall 0.117% 1,887/1,613,674 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.18%	46
Remaining individualsnot grpmax-eligible	0.176%	568
Admixed American	0.167%	600
Middle Eastern	0.149%	670
South Asian	0.0132%	7,589
European (non-Finnish)	0.00195%	51,300

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.Lys412Arg
Coding: c.1235A>G
MANE Select: NM_152612
dbSNP: rs148692511
Type: single nucleotide variant
Location: chr22:21636463 (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 c.73-8C>T Benign ★★ same type
CCDC116 p.Arg174= Benign ★★ same type
CCDC116 p.Asn302= Benign ★★ same type
CCDC116 p.Pro293Leu 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-lys412arg (accessed [today's date]).

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