Is CIART p.Pro356Ser (c.1066C>T) pathogenic?

CIART p.Pro356Ser (c.1066C>T) is classified Uncertain significance in CIART (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.1161); Ultra-rare (popmax 0.0548%, afr).

How common is CIART p.Pro356Ser (c.1066C>T) in the general population?

CIART p.Pro356Ser (c.1066C>T) is ultra-rare (popmax 0.0548%, afr) (gnomAD).

What do computational predictors say about CIART p.Pro356Ser (c.1066C>T)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

CIART p.Pro356Ser

c.1066C>T · VCV3492860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0548%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.35	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 -0.15	GERP -2.5
Regional constraint	o/e 0.92	unconstrained · MANE · 3,683 bp · p 0.082 · regional, not allelic
Overall
CADD	17.82	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 0.0548% African / African-American · 41/74,882 alleles

Filtering AF 0.0414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0368%

Overall 0.00304% 49/1,612,772 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0548%	1,826
Remaining individualsnot grpmax-eligible	0.00641%	15,611
Admixed American	0.00501%	19,971
South Asian	0.0011%	91,012

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.Pro356Ser
Coding: c.1066C>T
MANE Select: NM_144697
Type: single nucleotide variant
Location: chr1:150286862 (GRCh38)
Gene constraint: LOEUF 0.606 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 55.07

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

Similar variants

CIART p.Pro356His Uncertain significance ★ ⚠ same residue
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

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-pro356ser (accessed [today's date]).

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