Is CIC p.Asp1091Val (c.3272A>T) pathogenic?

CIC p.Asp1091Val (c.3272A>T) is classified Uncertain significance in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-19). AlphaMissense: likely pathogenic (0.9546); Very rare (popmax 0.0011%, sas).

How common is CIC p.Asp1091Val (c.3272A>T) in the general population?

CIC p.Asp1091Val (c.3272A>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CIC p.Asp1091Val (c.3272A>T)?

AlphaMissense predicts likely pathogenic (score 0.9546) — an in-silico prediction, not a clinical call.

CIC p.Asp1091Val

c.3272A>T · VCV4942612

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.9546	likely pathogenic
REVEL	0.402	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Overall
CADD	27.3	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 D182V vs ClinVar D1091V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,074 alleles

Overall 6.2e-05% 1/1,613,912 alleles · very rare exomes 1/1,461,734 · genomes 0/152,178 · joint denominator

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.Asp1091Val
Coding: c.3272A>T
MANE Select: NM_001386298
Type: single nucleotide variant
Location: chr19:42287412 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Similar variants

CIC p.Asp1091Asn Uncertain significance ★ ⚠ 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-asp1091val (accessed [today's date]).

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