Is CCDC70 p.Met44Leu (c.130A>C) pathogenic?

CCDC70 p.Met44Leu (c.130A>C) is classified Uncertain significance in CCDC70 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1944); Absent from gnomAD v4.1.

How common is CCDC70 p.Met44Leu (c.130A>C) in the general population?

CCDC70 p.Met44Leu (c.130A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC70 p.Met44Leu (c.130A>C)?

AlphaMissense predicts likely benign (score 0.1944) — an in-silico prediction, not a clinical call.

CCDC70 p.Met44Leu

c.130A>C · VCV4221455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1944 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1944	likely benign
REVEL	0.014	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 5.1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 665 bp · p 0.026 · regional, not allelic
Overall
CADD	18.77	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 M55L vs ClinVar M44L) — verify the residue.

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: CCDC70
Protein: p.Met44Leu
Coding: c.130A>C
MANE Select: NM_031290
Type: single nucleotide variant
Location: chr13:51865541 (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-met44leu (accessed [today's date]).

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