Is IFT122 p.Val778Phe (c.2332G>T) pathogenic?

IFT122 p.Val778Phe (c.2332G>T) is classified Uncertain significance in IFT122 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-10). AlphaMissense: likely benign (0.1036); Very rare (popmax 0.00167%, amr); Associated with cranioectodermal dysplasia 1.

What condition is associated with IFT122 p.Val778Phe (c.2332G>T)?

IFT122 p.Val778Phe (c.2332G>T) is associated with cranioectodermal dysplasia 1 (ClinVar).

How common is IFT122 p.Val778Phe (c.2332G>T) in the general population?

IFT122 p.Val778Phe (c.2332G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about IFT122 p.Val778Phe (c.2332G>T)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

IFT122 p.Val778Phe

c.2332G>T · rs139943115 · VCV1500941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cranioectodermal dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.8	GERP -3.6
Regional constraint	o/e 0.99	unconstrained · MANE · 26 kb · p 0.77 · regional, not allelic
Overall
CADD	5.47	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 0.00167% Admixed American · 1/60,032 alleles

Overall 6.19e-05% 1/1,614,238 alleles · very rare exomes 1/1,461,892 · genomes 0/152,346 · 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.Val778Phe
Coding: c.2332G>T
MANE Select: NM_052989
dbSNP: rs139943115
Type: single nucleotide variant
Location: chr3:129500025 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 778: an α-helix

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-val778phe (accessed [today's date]).

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