Is CCDC86 p.Arg337Cys (c.1009C>T) pathogenic?

CCDC86 p.Arg337Cys (c.1009C>T) is classified Uncertain significance in CCDC86 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: ambiguous (0.5542); Very rare (popmax 0.00223%, eas).

How common is CCDC86 p.Arg337Cys (c.1009C>T) in the general population?

CCDC86 p.Arg337Cys (c.1009C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CCDC86 p.Arg337Cys (c.1009C>T)?

AlphaMissense predicts ambiguous (score 0.5542) — an in-silico prediction, not a clinical call.

CCDC86 p.Arg337Cys

c.1009C>T · rs771726549 · VCV2315920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.5542	ambiguous
REVEL	0.55	indeterminate
SaProt	LLR -12.42	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,197 bp · p 0.43 · regional, not allelic
Overall
CADD	33.0	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 0.00223% East Asian · 1/44,872 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00192% 28/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,254
East Asiangrpmax	0.00223%	44,872
European (non-Finnish)	0.00195%	51,306
African / African-American	0.00133%	75,068
South Asian	0.0011%	91,082

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCDC86
Protein: p.Arg337Cys
Coding: c.1009C>T
MANE Select: NM_024098
dbSNP: rs771726549
Type: single nucleotide variant
Location: chr11:60850251 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 10 PDB
Residue 337: the 'disordered' region; an α-helix

Full CCDC86 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC86 p.Arg337His Uncertain significance ★ ⚠ same residue
CCDC86 p.Ala139Thr Uncertain significance ★ ⚠ same type
CCDC86 p.Ala139Val Uncertain significance ★ ⚠ same type
CCDC86 p.Ala149Gly Uncertain significance ★ ⚠ same type
CCDC86 p.Ala149Thr Uncertain significance ★ ⚠ same type
CCDC86 p.Ala169Gly Uncertain significance ★ ⚠ same type
CCDC86 p.Ala169Pro Uncertain significance ★ ⚠ same type
CCDC86 p.Ala358Pro 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/ccdc86-p-arg337cys (accessed [today's date]).

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