Is CCDC190 p.Phe69Ser (c.206T>C) pathogenic?

CCDC190 p.Phe69Ser (c.206T>C) is classified Uncertain significance in CCDC190 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely benign (0.1884); Ultra-rare (popmax 0.0329%, mid).

How common is CCDC190 p.Phe69Ser (c.206T>C) in the general population?

CCDC190 p.Phe69Ser (c.206T>C) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CCDC190 p.Phe69Ser (c.206T>C)?

AlphaMissense predicts likely benign (score 0.1884) — an in-silico prediction, not a clinical call.

CCDC190 p.Phe69Ser

c.206T>C · rs750622469 · VCV3139021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1884 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1884	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -2.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -2.5, phastCons 0.016
Regional constraint	o/e 1.06	unconstrained · MANE · 4,878 bp · p 0.27 · regional, not allelic
Overall
CADD	19.2	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 F70S vs ClinVar F69S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,076 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000934% 15/1,606,338 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,038
Remaining individualsnot grpmax-eligible	0.00965%	10,367
African / African-American	0.00936%	10,689

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: CCDC190
Protein: p.Phe69Ser
Coding: c.206T>C
MANE Select: NM_001394065
dbSNP: rs750622469
Type: single nucleotide variant
Location: chr1:162855737 (GRCh38)
Gene constraint: LOEUF 1.224 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.14

Full CCDC190 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC190 p.Ala107Thr Uncertain significance ★ ⚠ same type
CCDC190 p.Ala24Thr Uncertain significance ★ ⚠ same type
CCDC190 p.Arg259Gly Uncertain significance ★ ⚠ same type
CCDC190 p.Arg259Trp Uncertain significance ★ ⚠ same type
CCDC190 p.Arg7Lys Uncertain significance ★ ⚠ same type
CCDC190 p.Asp160Tyr Uncertain significance ★ ⚠ same type
CCDC190 p.Asp169Tyr Uncertain significance ★ ⚠ same type
CCDC190 p.Asp218Gly 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/ccdc190-p-phe69ser (accessed [today's date]).

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