Is IFT43 p.Ser42Phe (c.125C>T) pathogenic?

IFT43 p.Ser42Phe (c.125C>T) is classified Uncertain significance in IFT43 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-22). AlphaMissense: likely benign (0.1182); Very rare (popmax 8.47e-05%, nfe).

How common is IFT43 p.Ser42Phe (c.125C>T) in the general population?

IFT43 p.Ser42Phe (c.125C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about IFT43 p.Ser42Phe (c.125C>T)?

AlphaMissense predicts likely benign (score 0.1182) — an in-silico prediction, not a clinical call.

IFT43 p.Ser42Phe

c.125C>T · rs2503039960 · VCV2001980

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1182 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1182	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -7.95	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 2.9	GERP 0.14, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 98 kb · p 0.62 · regional, not allelic
Overall
CADD	24.5	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 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 6.2e-05% 1/1,613,882 alleles · very rare exomes 1/1,461,740 · genomes 0/152,142 · 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: IFT43
Protein: p.Ser42Phe
Coding: c.125C>T
MANE Select: NM_001102564
dbSNP: rs2503039960
Type: single nucleotide variant
Location: chr14:75988955 (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 42: the 'disordered' region

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

Similar variants

IFT43 p.Ser42= Likely benign ★ same residue
IFT43 c.148-2A>C Likely pathogenic ★★ same type
IFT43 c.296-5698C>T Likely pathogenic ★★ same type
IFT43 c.296-5681A>G Uncertain significance ★★ same type
IFT43 c.296-5697G>A Uncertain significance ★★ same type
IFT43 c.444+5G>A Uncertain significance ★★ same type
IFT43 p.Ala162Thr Uncertain significance ★★ ⚠ same type
IFT43 p.Ala162Val Uncertain significance ★★ ⚠ same type

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-ser42phe (accessed [today's date]).

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