Is CIT p.Tyr585= (c.1755C>T) pathogenic?

CIT p.Tyr585= (c.1755C>T) is classified Likely benign in CIT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). Very rare (popmax 0.00549%, sas).

How common is CIT p.Tyr585= (c.1755C>T) in the general population?

CIT p.Tyr585= (c.1755C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

CIT p.Tyr585=

c.1755C>T · rs764053689 · VCV1675514

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.546	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -3.2
Overall
CADD	1.995	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,080 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00161% 26/1,613,896 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
Remaining individualsnot grpmax-eligible	0.0064%	15,622
South Asiangrpmax	0.00549%	18,216
East Asian	0.00446%	22,440
African / African-American	0.00267%	37,450
European (non-Finnish)	0.000763%	131,113

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr585=
Coding: c.1755C>T
MANE Select: NM_001206999
dbSNP: rs764053689
Type: single nucleotide variant
Location: chr12:119776753 (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-tyr585 (accessed [today's date]).

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