Is CCDC83 p.Lys236Arg (c.707A>G) pathogenic?

CCDC83 p.Lys236Arg (c.707A>G) is classified Uncertain significance in CCDC83 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: likely benign (0.0856); Ultra-rare (popmax 0.0222%, nfe).

How common is CCDC83 p.Lys236Arg (c.707A>G) in the general population?

CCDC83 p.Lys236Arg (c.707A>G) is ultra-rare (popmax 0.0222%, nfe) (gnomAD).

What do computational predictors say about CCDC83 p.Lys236Arg (c.707A>G)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

CCDC83 p.Lys236Arg

c.707A>G · rs137945995 · VCV3139463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0222%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.15	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 11	GERP 0.38, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 54 kb · p 0.043 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0222% European (non-Finnish) · 262/1,178,552 alleles

Filtering AF 0.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0191%

Overall 0.0172% 277/1,611,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0222%	4,498
Remaining individualsnot grpmax-eligible	0.0112%	8,911
African / African-American	0.00535%	18,709
Finnishnot grpmax-eligible	0.00469%	21,319
Admixed American	0.00168%	59,662

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: CCDC83
Protein: p.Lys236Arg
Coding: c.707A>G
MANE Select: NM_001286159
dbSNP: rs137945995
Type: single nucleotide variant
Location: chr11:85911315 (GRCh38)
Gene constraint: LOEUF 1.263 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.76

Full CCDC83 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC83 c.794+1269C>G Uncertain significance ★ same type
CCDC83 c.794+1294T>C Uncertain significance ★ same type
CCDC83 c.794+1326G>A Uncertain significance ★ same type
CCDC83 c.794+1332C>T Uncertain significance ★ same type
CCDC83 p.Ala149Val Uncertain significance ★ ⚠ same type
CCDC83 p.Ala166Thr Uncertain significance ★ ⚠ same type
CCDC83 p.Ala39Gly Uncertain significance ★ ⚠ same type
CCDC83 p.Ala98Val 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/ccdc83-p-lys236arg (accessed [today's date]).

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