Is IFT122 p.Pro186Ser (c.556C>T) pathogenic?

IFT122 p.Pro186Ser (c.556C>T) is classified Uncertain significance in IFT122 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-02). AlphaMissense: likely pathogenic (0.6754); Absent from gnomAD v4.1; Associated with cranioectodermal dysplasia 1.

What condition is associated with IFT122 p.Pro186Ser (c.556C>T)?

IFT122 p.Pro186Ser (c.556C>T) is associated with cranioectodermal dysplasia 1 (ClinVar).

How common is IFT122 p.Pro186Ser (c.556C>T) in the general population?

IFT122 p.Pro186Ser (c.556C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT122 p.Pro186Ser (c.556C>T)?

AlphaMissense predicts likely pathogenic (score 0.6754) — an in-silico prediction, not a clinical call.

IFT122 p.Pro186Ser

c.556C>T · rs2108118912 · VCV1389923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6754 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

cranioectodermal dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.6754	likely pathogenic
REVEL	0.348	indeterminate
SaProt	LLR -3.41	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 25 kb · p 4.4e-05 · regional, not allelic
Overall
CADD	26.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IFT122
Protein: p.Pro186Ser
Coding: c.556C>T
MANE Select: NM_052989
dbSNP: rs2108118912
Type: single nucleotide variant
Location: chr3:129464774 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.91 · 5 PDB

Full IFT122 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cranioectodermal dysplasia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IFT122 c.1148-1G>C Pathogenic/Likely pathogenic ★★ same condition
IFT122 c.272+1G>A Likely pathogenic ★★ same condition
IFT122 c.273-257C>A Pathogenic/Likely pathogenic ★★ same condition
IFT122 c.3265+1G>A Pathogenic/Likely pathogenic ★★ same condition
IFT122 p.Arg1185Ter Pathogenic/Likely pathogenic ★★ same condition
IFT122 p.Arg189Ter Pathogenic/Likely pathogenic ★★ same condition
IFT122 p.Arg673Ter Pathogenic/Likely pathogenic ★★ same condition
IFT122 p.Gln1005Ter 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/ift122-p-pro186ser (accessed [today's date]).

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