Is CCIN p.Phe235Ser (c.704T>C) pathogenic?

CCIN p.Phe235Ser (c.704T>C) is classified Uncertain significance in CCIN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-20). AlphaMissense: likely benign (0.1526); Absent from gnomAD v4.1.

How common is CCIN p.Phe235Ser (c.704T>C) in the general population?

CCIN p.Phe235Ser (c.704T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCIN p.Phe235Ser (c.704T>C)?

AlphaMissense predicts likely benign (score 0.1526) — an in-silico prediction, not a clinical call.

CCIN p.Phe235Ser

c.704T>C · rs2489366875 · VCV2526894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1526 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1526	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -4.95	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 4.5	GERP -0.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,763 bp · p 7.5e-07 · regional, not allelic
Overall
CADD	15.61	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.

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: CCIN
Protein: p.Phe235Ser
Coding: c.704T>C
MANE Select: NM_005893
dbSNP: rs2489366875
Type: single nucleotide variant
Location: chr9:36170206 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 90.53
Residue 235: the back domain

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

Similar variants

CCIN p.Arg485Trp Benign/Likely benign ★★ ⚠ same type
CCIN p.Ala197Val Uncertain significance ★ ⚠ same type
CCIN p.Ala200Glu Uncertain significance ★ ⚠ same type
CCIN p.Ala200Thr Uncertain significance ★ ⚠ same type
CCIN p.Ala299Val Uncertain significance ★ ⚠ same type
CCIN p.Ala417Thr Uncertain significance ★ ⚠ same type
CCIN p.Ala536Ser Uncertain significance ★ ⚠ same type
CCIN p.Arg106Leu 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/ccin-p-phe235ser (accessed [today's date]).

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