Is IFT122 p.Ser76= (c.228C>T) pathogenic?

IFT122 p.Ser76= (c.228C>T) is classified Conflicting classifications of pathogenicity in IFT122 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-31). Ultra-rare (popmax 0.0178%, eas); Associated with cranioectodermal dysplasia 1.

What condition is associated with IFT122 p.Ser76= (c.228C>T)?

IFT122 p.Ser76= (c.228C>T) is associated with cranioectodermal dysplasia 1 (ClinVar).

How common is IFT122 p.Ser76= (c.228C>T) in the general population?

IFT122 p.Ser76= (c.228C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

IFT122 p.Ser76=

c.228C>T · rs772835552 · VCV343232

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

cranioectodermal dysplasia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.079	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.1	GERP -4.5
Overall
CADD	2.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,888 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00136% 22/1,613,932 alleles · ultra-rare exomes 14/1,461,760 · genomes 8/152,172 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,611
African / African-American	0.00401%	24,969
Remaining individualsnot grpmax-eligible	0.0032%	31,243
South Asian	0.0011%	91,086
European (non-Finnish)	0.000678%	147,495

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.Ser76=
Coding: c.228C>T
MANE Select: NM_052989
dbSNP: rs772835552
Type: single nucleotide variant
Location: chr3:129458633 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 76: a β-strand

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.Ser76Asn 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-ser76 (accessed [today's date]).

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