Is CIT p.Ala8Val (c.23C>T) pathogenic?

CIT p.Ala8Val (c.23C>T) is classified Uncertain significance in CIT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.0977); Ultra-rare (popmax 0.0394%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CIT p.Ala8Val (c.23C>T)?

CIT p.Ala8Val (c.23C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CIT p.Ala8Val (c.23C>T) in the general population?

CIT p.Ala8Val (c.23C>T) is ultra-rare (popmax 0.0394%, nfe) (gnomAD).

What do computational predictors say about CIT p.Ala8Val (c.23C>T)?

AlphaMissense predicts likely benign (score 0.0977) — an in-silico prediction, not a clinical call.

CIT p.Ala8Val

c.23C>T · rs143030033 · VCV1298560

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0977 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0394%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0977	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -3.9, phastCons 0.002
Regional constraint	o/e 0.96	unconstrained · MANE · 91 kb · p 0.38 · regional, not allelic
Overall
CADD	11.41	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0394% European (non-Finnish) · 465/1,179,708 alleles

Filtering AF 0.0365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0352%

Overall 0.0311% 502/1,613,480 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0394%	2,537
Middle Eastern	0.0329%	3,040
Remaining individualsnot grpmax-eligible	0.0256%	3,904
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,932
African / African-American	0.00801%	12,479
Admixed American	0.005%	19,987
Finnishnot grpmax-eligible	0.00469%	21,337
South Asian	0.0011%	91,028

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.Ala8Val
Coding: c.23C>T
MANE Select: NM_001206999
dbSNP: rs143030033
Type: single nucleotide variant
Location: chr12:119876146 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIT p.Arg1178Ter Pathogenic ★★ same condition
CIT c.4168+5G>A Uncertain significance ★★ same condition
CIT p.Ala1527Val Uncertain significance ★★ ⚠ same condition
CIT p.Ala495Ser Uncertain significance ★★ ⚠ same condition
CIT p.Arg100Gly Uncertain significance ★★ ⚠ same condition
CIT p.Arg1469Cys Uncertain significance ★★ ⚠ same condition
CIT p.Arg1861Cys Uncertain significance ★★ ⚠ same condition
CIT p.Arg2000His 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-ala8val (accessed [today's date]).

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