Is CIART p.Ser14Phe (c.41C>T) pathogenic?

CIART p.Ser14Phe (c.41C>T) is classified Uncertain significance in CIART (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.1326); Rare (popmax 0.583%, mid).

How common is CIART p.Ser14Phe (c.41C>T) in the general population?

CIART p.Ser14Phe (c.41C>T) is rare (popmax 0.583%, mid) (gnomAD).

What do computational predictors say about CIART p.Ser14Phe (c.41C>T)?

AlphaMissense predicts likely benign (score 0.1326) — an in-silico prediction, not a clinical call.

CIART p.Ser14Phe

c.41C>T · rs138047846 · VCV2356658

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1326 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.583%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1326	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -10.31	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,683 bp · p 0.082 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.583% Middle Eastern · 33/5,660 alleles

Filtering AF 0.427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.373%

Overall 0.0686% 1,053/1,534,956 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.583%	172
Admixed American	0.172%	582
Remaining individualsnot grpmax-eligible	0.0965%	1,036
Ashkenazi Jewishnot grpmax-eligible	0.0953%	1,050
South Asian	0.0867%	1,153
European (non-Finnish)	0.0682%	1,466
African / African-American	0.0111%	9,039
East Asian	0.00452%	22,144
Finnishnot grpmax-eligible	0.00328%	30,466

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.Ser14Phe
Coding: c.41C>T
MANE Select: NM_144697
dbSNP: rs138047846
Type: single nucleotide variant
Location: chr1:150283308 (GRCh38)
Gene constraint: LOEUF 0.606 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 55.07
Residue 14: 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-ser14phe (accessed [today's date]).

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