Is CIT p.Ile1723= (c.5169T>A) pathogenic?

CIT p.Ile1723= (c.5169T>A) is classified Benign in CIT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-23). Low-frequency (popmax 3.12%, nfe).

How common is CIT p.Ile1723= (c.5169T>A) in the general population?

CIT p.Ile1723= (c.5169T>A) is low-frequency (popmax 3.12%, nfe) (gnomAD).

CIT p.Ile1723=

c.5169T>A · rs56167781 · VCV1246883

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.12%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.177	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -3.6, phastCons 0.008
Overall
CADD	1.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.12% European (non-Finnish) · 36,660/1,176,012 alleles

Filtering AF 3.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.08%

Overall 2.5% 40,140/1,604,714 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.73%	21
European (non-Finnish)grpmax	3.12%	32
Remaining individualsnot grpmax-eligible	1.96%	51
Finnishnot grpmax-eligible	1.47%	68
Admixed American	0.803%	125
African / African-American	0.48%	208
South Asian	0.473%	211
Middle Eastern	0.182%	550
Ashkenazi Jewishnot grpmax-eligible	0.0509%	1,964
East Asian	0.00456%	21,949

Amish 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.Ile1723=
Coding: c.5169T>A
MANE Select: NM_001206999
dbSNP: rs56167781
Type: single nucleotide variant
Location: chr12:119708221 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 1723: the cnh domain

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

Similar variants

CIT p.Ile1723Val Benign ★★ same residue
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

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-ile1723 (accessed [today's date]).

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