Is CIT p.Ala807Val (c.2420C>T) pathogenic?

CIT p.Ala807Val (c.2420C>T) is classified Uncertain significance in CIT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-01). AlphaMissense: ambiguous (0.5312); Very rare (popmax 0.0055%, sas).

How common is CIT p.Ala807Val (c.2420C>T) in the general population?

CIT p.Ala807Val (c.2420C>T) is very rare (popmax 0.0055%, sas) (gnomAD).

What do computational predictors say about CIT p.Ala807Val (c.2420C>T)?

AlphaMissense predicts ambiguous (score 0.5312) — an in-silico prediction, not a clinical call.

CIT p.Ala807Val

c.2420C>T · rs749312866 · VCV2643391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5312 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0055%, sas)

Computational evidence

Protein change
AlphaMissense	0.5312	ambiguous
REVEL	0.294	indeterminate
SaProt	LLR -6.86	tolerated
Splicing
SpliceAI	Δ0.58	donor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 55 kb · p 2.1e-24 · regional, not allelic
Overall
CADD	35.0	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 A765V vs ClinVar A807V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0055% South Asian · 5/90,952 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00118% 19/1,606,224 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0055%	18,190
African / African-American	0.00268%	37,376
East Asian	0.00223%	44,856
European (non-Finnish)	0.000938%	106,626

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.Ala807Val
Coding: c.2420C>T
MANE Select: NM_001206999
dbSNP: rs749312866
Type: single nucleotide variant
Location: chr12:119760940 (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

Similar variants

CIT p.Arg1178Ter Pathogenic ★★ same type
CIT p.Arg220Ter Pathogenic ★★ same type
CIT c.4168+5G>A Uncertain significance ★★ same type
CIT p.Ala1144Thr Uncertain significance ★★ ⚠ same type
CIT p.Ala1466Asp Uncertain significance ★★ ⚠ same type
CIT p.Ala1527Val Uncertain significance ★★ ⚠ same type
CIT p.Ala244Val Uncertain significance ★★ ⚠ same type
CIT p.Ala495Ser Uncertain significance ★★ ⚠ 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/cit-p-ala807val (accessed [today's date]).

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