Is IFT122 p.Asp1237Asn (c.3709G>A) pathogenic?

IFT122 p.Asp1237Asn (c.3709G>A) is classified Uncertain significance in IFT122 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-10). AlphaMissense: likely benign (0.093); Very rare (popmax 0.000678%, nfe); Associated with cranioectodermal dysplasia 1.

What condition is associated with IFT122 p.Asp1237Asn (c.3709G>A)?

IFT122 p.Asp1237Asn (c.3709G>A) is associated with cranioectodermal dysplasia 1 (ClinVar).

How common is IFT122 p.Asp1237Asn (c.3709G>A) in the general population?

IFT122 p.Asp1237Asn (c.3709G>A) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about IFT122 p.Asp1237Asn (c.3709G>A)?

AlphaMissense predicts likely benign (score 0.093) — an in-silico prediction, not a clinical call.

IFT122 p.Asp1237Asn

c.3709G>A · VCV3588509

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cranioectodermal dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.093	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.085, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 2,793 bp · p 0.11 · regional, not allelic
Overall
CADD	18.98	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 0.000678% European (non-Finnish) · 8/1,179,772 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000497% 8/1,609,768 alleles · very rare exomes 6/1,457,518 · genomes 2/152,250 · 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.Asp1237Asn
Coding: c.3709G>A
MANE Select: NM_052989
Type: single nucleotide variant
Location: chr3:129520248 (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 p.Asp1237= Uncertain significance ★ same residue
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

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-asp1237asn (accessed [today's date]).

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