Is CCDC70 p.Phe61Cys (c.182T>G) pathogenic?

CCDC70 p.Phe61Cys (c.182T>G) is classified Uncertain significance in CCDC70 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: ambiguous (0.3839); Very rare (popmax 0.00267%, afr).

How common is CCDC70 p.Phe61Cys (c.182T>G) in the general population?

CCDC70 p.Phe61Cys (c.182T>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CCDC70 p.Phe61Cys (c.182T>G)?

AlphaMissense predicts ambiguous (score 0.3839) — an in-silico prediction, not a clinical call.

CCDC70 p.Phe61Cys

c.182T>G · rs778245354 · VCV3139321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3839 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.3839	ambiguous · top 10% in CCDC70
REVEL	0.212	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.62, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 665 bp · p 0.026 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F72C vs ClinVar F61C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,916 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,614,044 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,458
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000508%	196,672

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.Phe61Cys
Coding: c.182T>G
MANE Select: NM_031290
dbSNP: rs778245354
Type: single nucleotide variant
Location: chr13:51865593 (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.Phe61Ser 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
CCDC70 p.Arg115His Uncertain significance ★ ⚠ same type
CCDC70 p.Arg136Gln 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-phe61cys (accessed [today's date]).

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