Is CIROP p.Ser384Leu (c.1151C>T) pathogenic?

CIROP p.Ser384Leu (c.1151C>T) is classified Pathogenic in CIROP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-03-15). AlphaMissense: ambiguous (0.4279); Very rare (popmax 0.00349%, afr); Associated with heterotaxy, visceral, 12, autosomal.

What condition is associated with CIROP p.Ser384Leu (c.1151C>T)?

CIROP p.Ser384Leu (c.1151C>T) is associated with heterotaxy, visceral, 12, autosomal (ClinVar).

How common is CIROP p.Ser384Leu (c.1151C>T) in the general population?

CIROP p.Ser384Leu (c.1151C>T) is very rare (popmax 0.00349%, afr) (gnomAD).

What do computational predictors say about CIROP p.Ser384Leu (c.1151C>T)?

AlphaMissense predicts ambiguous (score 0.4279) — an in-silico prediction, not a clinical call.

CIROP p.Ser384Leu

c.1151C>T · rs183023758 · VCV1344488

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4279 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00349%, afr)

Conditions

heterotaxy, visceral, 12, autosomal

Computational evidence

Protein change
AlphaMissense	0.4279	ambiguous
SaProt	LLR -12.18	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 2, phastCons 1
Regional constraint	o/e 1.77	unconstrained · MANE · 5,635 bp · p 1.3e-32 · regional, not allelic
Overall
CADD	24.0	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 0.00349% African / African-American · 2/57,374 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00122%

Overall 0.00199% 14/702,964 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00349%	28,687
European (non-Finnish)	0.00286%	34,997
East Asian	0.00268%	37,282

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: CIROP
Protein: p.Ser384Leu
Coding: c.1151C>T
MANE Select: NM_001354640
dbSNP: rs183023758
Type: single nucleotide variant
Location: chr14:23102250 (GRCh38)
Structure: AlphaFold pLDDT 73.73
Residue 384: a UniProt-annotated variant site (in htx12); a UniProt-annotated variant site (in htx12; uncertain significance)

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

Disease context

heterotaxy, visceral, 12, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIROP p.Gln528Ter Likely pathogenic ★ same condition
CIROP p.Arg22Ter Conflicting classifications of pathogenicity ★ same condition
CIROP p.Gly180Arg Uncertain significance ★ ⚠ same condition
CIROP p.Gly511Glu Uncertain significance ★ same condition
CIROP p.Ser31Phe Conflicting classifications of pathogenicity ★ ⚠ same condition
CIROP p.Tyr68Cys Uncertain significance ★ ⚠ same condition
CIROP p.Arg191Ter Pathogenic same condition
CIROP p.Arg389Ile Pathogenic same condition

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/cirop-p-ser384leu (accessed [today's date]).

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