Is CCDC6 p.Ser419Arg (c.1257T>A) pathogenic?

CCDC6 p.Ser419Arg (c.1257T>A) is classified Uncertain significance in CCDC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely pathogenic (0.9946); Absent from gnomAD v4.1.

How common is CCDC6 p.Ser419Arg (c.1257T>A) in the general population?

CCDC6 p.Ser419Arg (c.1257T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC6 p.Ser419Arg (c.1257T>A)?

AlphaMissense predicts likely pathogenic (score 0.9946) — an in-silico prediction, not a clinical call.

CCDC6 p.Ser419Arg

c.1257T>A · rs764143588 · VCV2623517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9946	likely pathogenic
REVEL	0.31	indeterminate
SaProt	LLR -10.38	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -5.5
Regional constraint	o/e 0.12	constrained · MANE · 31 bp · p 0.00038 · regional, not allelic
Overall
CADD	18.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC6
Protein: p.Ser419Arg
Coding: c.1257T>A
MANE Select: NM_005436
dbSNP: rs764143588
Type: single nucleotide variant
Location: chr10:59793085 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 76.03 · 2 PDB
Residue 419: 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-ser419arg (accessed [today's date]).

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