Is IFT122 p.Ser322Phe (c.965C>T) pathogenic?

IFT122 p.Ser322Phe (c.965C>T) is classified Likely pathogenic in IFT122 (ClinVar, Single submitter, 3 submitters; last evaluated 2010-03-02). AlphaMissense: likely pathogenic (0.6712); Very rare (popmax 0.000681%); Associated with cranioectodermal dysplasia 1.

What condition is associated with IFT122 p.Ser322Phe (c.965C>T)?

IFT122 p.Ser322Phe (c.965C>T) is associated with cranioectodermal dysplasia 1 (ClinVar).

How common is IFT122 p.Ser322Phe (c.965C>T) in the general population?

IFT122 p.Ser322Phe (c.965C>T) is very rare (popmax 0.000681%) (gnomAD).

What do computational predictors say about IFT122 p.Ser322Phe (c.965C>T)?

AlphaMissense predicts likely pathogenic (score 0.6712) — an in-silico prediction, not a clinical call.

IFT122 p.Ser322Phe

c.965C>T · rs267607192 · VCV4636

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6712 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000681%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

cranioectodermal dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.6712	likely pathogenic ✓ concordant with ClinVar
REVEL	0.511	indeterminate
SaProt	LLR -11.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; 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 2.2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 25 kb · p 4.4e-05 · regional, not allelic
Overall
CADD	27.5	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 0.000681%

Overall 0.000681% 11/1,614,104 alleles · very rare exomes 11/1,461,890 · genomes 0/152,214 · joint denominator

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: IFT122
Protein: p.Ser322Phe
Coding: c.965C>T
MANE Select: NM_052989
dbSNP: rs267607192
Type: single nucleotide variant
Location: chr3:129476463 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 322: a UniProt-annotated variant site (in ced1; no effect on interaction with itf43:wdr35)

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-ser322phe (accessed [today's date]).

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