Is CCDC70 p.Glu78Lys (c.232G>A) pathogenic?

CCDC70 p.Glu78Lys (c.232G>A) is classified Uncertain significance in CCDC70 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.0885); Ultra-rare (popmax 0.0165%, mid).

How common is CCDC70 p.Glu78Lys (c.232G>A) in the general population?

CCDC70 p.Glu78Lys (c.232G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CCDC70 p.Glu78Lys (c.232G>A)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

CCDC70 p.Glu78Lys

c.232G>A · VCV4221450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.016	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 4.7	GERP 0.76, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 665 bp · p 0.026 · regional, not allelic
Overall
CADD	21.4	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 E89K vs ClinVar E78K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00397% 64/1,614,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.0121%	8,281
East Asian	0.00668%	14,963
Remaining individualsnot grpmax-eligible	0.0064%	15,623
European (non-Finnish)	0.00381%	26,222

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.Glu78Lys
Coding: c.232G>A
MANE Select: NM_031290
Type: single nucleotide variant
Location: chr13:51865643 (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 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
CCDC70 p.Arg115His Uncertain significance ★ ⚠ same type
CCDC70 p.Arg136Gln Uncertain significance ★ ⚠ same type
CCDC70 p.Arg136Trp 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-glu78lys (accessed [today's date]).

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