Is CIART p.Arg83Gln (c.248G>A) pathogenic?

CIART p.Arg83Gln (c.248G>A) is classified Uncertain significance in CIART (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.0753); Ultra-rare (popmax 0.0308%, nfe).

How common is CIART p.Arg83Gln (c.248G>A) in the general population?

CIART p.Arg83Gln (c.248G>A) is ultra-rare (popmax 0.0308%, nfe) (gnomAD).

What do computational predictors say about CIART p.Arg83Gln (c.248G>A)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

CIART p.Arg83Gln

c.248G>A · rs142518963 · VCV2305598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0308%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.064	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
Pangolin	Δ0.25	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.7	GERP -2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,683 bp · p 0.082 · regional, not allelic
Overall
CADD	19.88	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 0.0308% European (non-Finnish) · 364/1,180,052 alleles

Filtering AF 0.0282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0272%

Overall 0.0237% 382/1,614,104 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0308%	3,242
Remaining individualsnot grpmax-eligible	0.0128%	7,811
African / African-American	0.00801%	12,488
Admixed American	0.005%	20,003
East Asian	0.00223%	44,886

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: CIART
Protein: p.Arg83Gln
Coding: c.248G>A
MANE Select: NM_144697
dbSNP: rs142518963
Type: single nucleotide variant
Location: chr1:150283515 (GRCh38)
Gene constraint: LOEUF 0.606 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 55.07
Residue 83: the 'disordered' region

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

Similar variants

CIART p.Gln162= Benign ★★ same type
CIART p.Ala255Pro Uncertain significance ★ ⚠ same type
CIART p.Ala255Val Uncertain significance ★ ⚠ same type
CIART p.Ala359Pro Uncertain significance ★ ⚠ same type
CIART p.Ala377Val Uncertain significance ★ ⚠ same type
CIART p.Ala380Ser Uncertain significance ★ ⚠ same type
CIART p.Arg160Ser Uncertain significance ★ ⚠ same type
CIART p.Arg367Gln 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/ciart-p-arg83gln (accessed [today's date]).

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