Is CCDC70 p.Phe61Ser (c.182T>C) pathogenic?

CCDC70 p.Phe61Ser (c.182T>C) is classified Uncertain significance in CCDC70 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: ambiguous (0.4333); Very rare (popmax 0.000424%, nfe).

How common is CCDC70 p.Phe61Ser (c.182T>C) in the general population?

CCDC70 p.Phe61Ser (c.182T>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CCDC70 p.Phe61Ser (c.182T>C)?

AlphaMissense predicts ambiguous (score 0.4333) — an in-silico prediction, not a clinical call.

CCDC70 p.Phe61Ser

c.182T>C · VCV4221457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4333	ambiguous · top 8% in CCDC70
REVEL	0.259	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 F72S vs ClinVar F61S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,022 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00041% 6/1,461,838 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,040
European (non-Finnish)grpmax	0.000424%	236,004

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe61Ser
Coding: c.182T>C
MANE Select: NM_031290
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.Phe61Cys 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-phe61ser (accessed [today's date]).

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