Is CCDC6 p.Ser19Asn (c.56G>A) pathogenic?

CCDC6 p.Ser19Asn (c.56G>A) is classified Uncertain significance in CCDC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: likely benign (0.1736); Ultra-rare (popmax 0.0117%, amr).

How common is CCDC6 p.Ser19Asn (c.56G>A) in the general population?

CCDC6 p.Ser19Asn (c.56G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about CCDC6 p.Ser19Asn (c.56G>A)?

AlphaMissense predicts likely benign (score 0.1736) — an in-silico prediction, not a clinical call.

CCDC6 p.Ser19Asn

c.56G>A · VCV3997076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1736 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1736	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -7.96	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 6.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 144 bp · p 0.64 · regional, not allelic
Overall
CADD	24.1	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 0.0117% Admixed American · 7/59,744 alleles

Filtering AF 0.00545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00382%

Overall 0.000555% 8/1,441,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,535
East Asian	0.00224%	44,636

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: CCDC6
Protein: p.Ser19Asn
Coding: c.56G>A
MANE Select: NM_005436
Type: single nucleotide variant
Location: chr10:59906369 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 76.03 · 2 PDB
Residue 19: the 'disordered' region

Full CCDC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC6 p.Leu206= Benign ★★ same type
CCDC6 p.Ala13Thr Uncertain significance ★ ⚠ same type
CCDC6 p.Arg197Gln Uncertain significance ★ ⚠ same type
CCDC6 p.Arg271Gln Uncertain significance ★ ⚠ same type
CCDC6 p.Arg298Thr Uncertain significance ★ ⚠ same type
CCDC6 p.Arg415Gln Uncertain significance ★ ⚠ same type
CCDC6 p.Asn267Ser Uncertain significance ★ ⚠ same type
CCDC6 p.Cys319Ser 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/ccdc6-p-ser19asn (accessed [today's date]).

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