Is CIC p.Ser2013Thr (c.6037T>A) pathogenic?

CIC p.Ser2013Thr (c.6037T>A) is classified Benign/Likely benign in CIC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-07). AlphaMissense: likely benign (0.0905); Low-frequency (popmax 1.54%, eas).

How common is CIC p.Ser2013Thr (c.6037T>A) in the general population?

CIC p.Ser2013Thr (c.6037T>A) is low-frequency (popmax 1.54%, eas) (gnomAD).

What do computational predictors say about CIC p.Ser2013Thr (c.6037T>A)?

AlphaMissense predicts likely benign (score 0.0905) — an in-silico prediction, not a clinical call.

CIC p.Ser2013Thr

c.6037T>A · rs185048610 · VCV133908

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0905 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.54%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0905	likely benign
REVEL	0.112	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.49, phastCons 1
Overall
CADD	22.0	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 S1104T vs ClinVar S2013T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.54% East Asian · 689/44,850 alleles

Filtering AF 1.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4%

Overall 0.0518% 836/1,613,574 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.54%	65
Remaining individualsnot grpmax-eligible	0.166%	601
African / African-American	0.0254%	3,944
Admixed American	0.0233%	4,287
South Asian	0.00549%	18,216
European (non-Finnish)	0.000424%	235,978

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.Ser2013Thr
Coding: c.6037T>A
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs185048610
Type: single nucleotide variant
Location: chr19:42292700 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Similar variants

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
SLC25A1 p.Ala274Val Pathogenic/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-ser2013thr (accessed [today's date]).

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