Is CIT p.Ser1359= (c.4077C>T) pathogenic?

CIT p.Ser1359= (c.4077C>T) is classified Benign in CIT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 31%, mid) — too common for a highly-penetrant pathogenic allele; Associated with microcephaly 17, primary, autosomal recessive.

What condition is associated with CIT p.Ser1359= (c.4077C>T)?

CIT p.Ser1359= (c.4077C>T) is associated with microcephaly 17, primary, autosomal recessive (ClinVar).

CIT p.Ser1359=

Q: How common is CIT p.Ser1359= (c.4077C>T) in the general population?

CIT p.Ser1359= (c.4077C>T) is common (popmax 31%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4077C>T · rs278102 · VCV1209741

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 31%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

microcephaly 17, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.287	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -3.6
Overall
CADD	5.675	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31% Middle Eastern · 1,877/6,062 alleles

Filtering AF 29.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.3%

Overall 26.4% 425,570/1,613,652 alleles · common exomes 388,313/1,461,572 · genomes 37,257/152,080 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	31%	3
European (non-Finnish)	28.7%	3
Remaining individualsnot grpmax-eligible	25.5%	4
Ashkenazi Jewishnot grpmax-eligible	25%	4
African / African-American	23.9%	4
Finnishnot grpmax-eligible	22.4%	4
South Asian	20.3%	5
Admixed American	17.8%	6
Amishnot grpmax-eligible	13%	8
East Asian	1.62%	62

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: CIT
Protein: p.Ser1359=
Coding: c.4077C>T
MANE Select: NM_001206999
dbSNP: rs278102
Type: single nucleotide variant
Location: chr12:119718336 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75

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

Disease context

microcephaly 17, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIT p.Arg220Ter Pathogenic ★★ same condition
CIT p.Ala1144Thr Uncertain significance ★★ ⚠ same condition
CIT p.Ala244Val Uncertain significance ★★ ⚠ same condition
CIT p.Arg1633Cys Uncertain significance ★★ ⚠ same condition
CIT p.Arg23Trp Uncertain significance ★★ ⚠ same condition
CIT p.Arg696Cys Uncertain significance ★★ same condition
CIT p.Asn1301Ser Uncertain significance ★★ ⚠ same condition
CIT p.Asn786Ser Uncertain significance ★★ ⚠ same condition

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/cit-p-ser1359 (accessed [today's date]).

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