Is CIC p.Pro1802Ser (c.5404C>T) pathogenic?

CIC p.Pro1802Ser (c.5404C>T) is classified Likely benign in CIC (ClinVar, Single submitter, 3 submitters; last evaluated 2020-01-03). AlphaMissense: likely benign (0.1144); Rare (popmax 0.223%, afr).

How common is CIC p.Pro1802Ser (c.5404C>T) in the general population?

CIC p.Pro1802Ser (c.5404C>T) is rare (popmax 0.223%, afr) (gnomAD).

What do computational predictors say about CIC p.Pro1802Ser (c.5404C>T)?

AlphaMissense predicts likely benign (score 0.1144) — an in-silico prediction, not a clinical call.

CIC p.Pro1802Ser

c.5404C>T · rs142397024 · VCV133900

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1144 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.223%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1144	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.21, phastCons 1
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P893S vs ClinVar P1802S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.223% African / African-American · 167/75,048 alleles

Filtering AF 0.195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.0115% 185/1,613,080 alleles · rare exomes 103/1,460,738 · genomes 82/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.223%	449
Remaining individualsnot grpmax-eligible	0.0128%	7,812
South Asian	0.0022%	45,543
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000593%	168,571

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: CIC
Protein: p.Pro1802Ser
Coding: c.5404C>T
MANE Select: NM_001386298
dbSNP: rs142397024
Type: single nucleotide variant
Location: chr19:42291445 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Similar variants

CIC p.Pro1802= Likely benign ★ same residue
CIC c.3179+1G>A Likely pathogenic ★★ same type
CIC c.3179+1G>T Pathogenic ★★ same type
CIC c.5903-2A>G Likely pathogenic ★★ same type
CIC p.Asn1136Ser Likely pathogenic ★★ same type
CIC p.Gln1134Ter Pathogenic ★★ same type
CIC p.Gln1799Ter Likely pathogenic ★★ same type
SLC25A1 c.821+1G>A Pathogenic ★★ 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/cic-p-pro1802ser (accessed [today's date]).

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