Is IFT43 p.Ala162= (c.486G>A) pathogenic?

IFT43 p.Ala162= (c.486G>A) is classified Benign/Likely benign in IFT43 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-29). Low-frequency (popmax 1.25%, eas); Associated with cranioectodermal dysplasia 3.

What condition is associated with IFT43 p.Ala162= (c.486G>A)?

IFT43 p.Ala162= (c.486G>A) is associated with cranioectodermal dysplasia 3, retinitis pigmentosa 81, short-rib thoracic dysplasia 18 with polydactyly (ClinVar).

How common is IFT43 p.Ala162= (c.486G>A) in the general population?

IFT43 p.Ala162= (c.486G>A) is low-frequency (popmax 1.25%, eas) (gnomAD).

IFT43 p.Ala162=

c.486G>A · rs143729954 · VCV732799

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.25%, eas)

Conditions

cranioectodermal dysplasia 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -15	GERP -5
Overall
CADD	0.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.25% East Asian · 559/44,874 alleles

Filtering AF 1.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.0467% 754/1,614,000 alleles · low-frequency exomes 641/1,461,772 · genomes 113/152,228 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.25%	80
Remaining individualsnot grpmax-eligible	0.128%	781
South Asian	0.0351%	2,846
Middle Eastern	0.0165%	6,062
African / African-American	0.00933%	10,716
Admixed American	0.00833%	12,005
European (non-Finnish)	0.00593%	16,856

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: IFT43
Protein: p.Ala162=
Coding: c.486G>A
MANE Select: NM_001102564
dbSNP: rs143729954
Type: single nucleotide variant
Location: chr14:76083268 (GRCh38)
Gene constraint: LOEUF 1.282 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.09 · 3 PDB
Residue 162: an α-helix

Full IFT43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cranioectodermal dysplasia 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 81 short-rib thoracic dysplasia 18 with polydactyly

Similar variants

IFT43 p.Ala162Val Uncertain significance ★★ ⚠ same residue
IFT43 p.Ala162Thr Uncertain significance ★★ ⚠ same residue
IFT43 c.148-2A>C Likely pathogenic ★★ same condition
IFT43 c.296-5698C>T Likely pathogenic ★★ same condition
IFT43 c.296-5681A>G Uncertain significance ★★ same condition
IFT43 c.296-5697G>A Uncertain significance ★★ same condition
IFT43 c.444+5G>A Uncertain significance ★★ same condition
IFT43 p.Ala202Val Uncertain significance ★★ ⚠ 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/ift43-p-ala162 (accessed [today's date]).

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