Is CIART p.Ser17Pro (c.49T>C) pathogenic?

CIART p.Ser17Pro (c.49T>C) is classified Uncertain significance in CIART (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-04). AlphaMissense: likely benign (0.0668); Very rare (popmax 0.00209%, amr).

How common is CIART p.Ser17Pro (c.49T>C) in the general population?

CIART p.Ser17Pro (c.49T>C) is very rare (popmax 0.00209%, amr) (gnomAD).

What do computational predictors say about CIART p.Ser17Pro (c.49T>C)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

CIART p.Ser17Pro

c.49T>C · VCV4228850

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00209%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -7.74	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 1.2	GERP -1.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,683 bp · p 0.082 · regional, not allelic
Overall
CADD	20.4	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 0.00209% Admixed American · 1/47,764 alleles

Filtering AF 0.000254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000163%

Overall 0.000519% 8/1,540,768 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00209%	47,764
European (non-Finnish)	0.000611%	163,784

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.Ser17Pro
Coding: c.49T>C
MANE Select: NM_144697
Type: single nucleotide variant
Location: chr1:150283316 (GRCh38)
Gene constraint: LOEUF 0.606 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 55.07
Residue 17: 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-ser17pro (accessed [today's date]).

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