Is CIC p.Gly1977Ser (c.5929G>A) pathogenic?

CIC p.Gly1977Ser (c.5929G>A) is classified Likely benign in CIC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0845); Rare (popmax 0.184%, sas); Associated with intellectual disability.

What condition is associated with CIC p.Gly1977Ser (c.5929G>A)?

CIC p.Gly1977Ser (c.5929G>A) is associated with intellectual disability (ClinVar).

How common is CIC p.Gly1977Ser (c.5929G>A) in the general population?

CIC p.Gly1977Ser (c.5929G>A) is rare (popmax 0.184%, sas) (gnomAD).

What do computational predictors say about CIC p.Gly1977Ser (c.5929G>A)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

CIC p.Gly1977Ser

c.5929G>A · rs370377701 · VCV133907

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.184%, sas)

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.351	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
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 G1068S vs ClinVar G1977S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.184% South Asian · 168/91,076 alleles

Filtering AF 0.162% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.0119% 192/1,613,258 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.184%	542
Middle Eastern	0.033%	3,029
Remaining individualsnot grpmax-eligible	0.016%	6,249
African / African-American	0.00533%	18,753
European (non-Finnish)	0.000678%	147,489

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.Gly1977Ser
Coding: c.5929G>A
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs370377701
Type: single nucleotide variant
Location: chr19:42292592 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIC p.Gly1977Ala Uncertain significance ★ ⚠ same residue
CIC p.Thr2151Ala Uncertain significance ★ ⚠ same condition
CIC c.7054+4C>A Likely benign ★ same condition
CIC p.Asn1583Ser Likely benign same condition
CIC p.Asn1611Asp Likely benign same condition
CIC p.Ser1041Cys Likely benign same condition
CIC c.3180-9_3180-5del Likely benign ★ same condition
CIC c.3179+1G>A Likely 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-gly1977ser (accessed [today's date]).

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