Is CCDC7 p.Arg855Cys (c.2563C>T) pathogenic?

CCDC7 p.Arg855Cys (c.2563C>T) is classified Uncertain significance in CCDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.1186); Ultra-rare (popmax 0.0511%, eas).

How common is CCDC7 p.Arg855Cys (c.2563C>T) in the general population?

CCDC7 p.Arg855Cys (c.2563C>T) is ultra-rare (popmax 0.0511%, eas) (gnomAD).

What do computational predictors say about CCDC7 p.Arg855Cys (c.2563C>T)?

AlphaMissense predicts likely benign (score 0.1186) — an in-silico prediction, not a clinical call.

CCDC7 p.Arg855Cys

c.2563C>T · rs372886513 · VCV2397717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1186 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0511%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1186	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -8.04	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 -20
Regional constraint	o/e 1.04	unconstrained · MANE · 425 kb · p 0.13 · regional, not allelic
Overall
CADD	14.76	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 0.0511% East Asian · 22/43,078 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0292%

Overall 0.00712% 110/1,544,618 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.107%	935
East Asiangrpmax	0.0511%	1,958
Admixed American	0.00588%	17,005
South Asian	0.00477%	20,957
African / African-American	0.00278%	35,936
European (non-Finnish)	0.00132%	75,734

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: CCDC7
Protein: p.Arg855Cys
Coding: c.2563C>T
MANE Select: NM_001395015
dbSNP: rs372886513
Type: single nucleotide variant
Location: chr10:32711724 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.53

Full CCDC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC7 c.3604+1G>C Uncertain significance ★ same type
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CCDC7 p.Arg209Cys Uncertain significance ★ ⚠ same type
CCDC7 p.Arg274Gln Uncertain significance ★ ⚠ same type
CCDC7 p.Asn12Ser Uncertain significance ★ ⚠ same type
CCDC7 p.Asn192Asp Uncertain significance ★ ⚠ same type
CCDC7 p.Asp1266Tyr Uncertain significance ★ ⚠ same type
CCDC7 p.Asp259Val 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/ccdc7-p-arg855cys (accessed [today's date]).

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