Is CCDC70 p.Arg213Ser (c.637C>A) pathogenic?

CCDC70 p.Arg213Ser (c.637C>A) is classified Uncertain significance in CCDC70 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.126); Ultra-rare (popmax 0.0126%, amr).

How common is CCDC70 p.Arg213Ser (c.637C>A) in the general population?

CCDC70 p.Arg213Ser (c.637C>A) is ultra-rare (popmax 0.0126%, amr) (gnomAD).

What do computational predictors say about CCDC70 p.Arg213Ser (c.637C>A)?

AlphaMissense predicts likely benign (score 0.126) — an in-silico prediction, not a clinical call.

CCDC70 p.Arg213Ser

c.637C>A · VCV4649629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.126 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.126	likely benign
REVEL	0.011	strongly benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.64	GERP -3
Regional constraint	o/e 1.14	unconstrained · MANE · 665 bp · p 0.026 · regional, not allelic
Overall
CADD	2.226	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R224S vs ClinVar R213S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0126% Admixed American · 7/55,742 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00414%

Overall 0.00201% 32/1,594,230 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0126%	7,963
Remaining individualsnot grpmax-eligible	0.00325%	30,756
European (non-Finnish)	0.00196%	50,956

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: CCDC70
Protein: p.Arg213Ser
Coding: c.637C>A
MANE Select: NM_031290
Type: single nucleotide variant
Location: chr13:51866048 (GRCh38)
Gene constraint: LOEUF 1.228 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.60

Full CCDC70 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC70 p.Arg213Cys Uncertain significance ★ ⚠ same residue
CCDC70 p.Arg213His Uncertain significance ★ ⚠ same residue
CCDC70 p.Arg213Leu Uncertain significance ★ ⚠ same residue
CCDC70 c.-14G>A Uncertain significance ★ ⚠ same type
CCDC70 c.-24C>T Uncertain significance ★ ⚠ same type
CCDC70 p.Ala208Thr Uncertain significance ★ ⚠ same type
CCDC70 p.Ala39Pro Uncertain significance ★ ⚠ same type
CCDC70 p.Ala39Ser 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/ccdc70-p-arg213ser (accessed [today's date]).

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