Is IFT172 p.His2= (c.6C>T) pathogenic?

IFT172 p.His2= (c.6C>T) is classified Likely benign in IFT172 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-27). Very rare (popmax 0.00416%, nfe); Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

How common is IFT172 p.His2= (c.6C>T) in the general population?

IFT172 p.His2= (c.6C>T) is very rare (popmax 0.00416%, nfe) (gnomAD).

IFT172 p.His2=

Q: What condition is associated with IFT172 p.His2= (c.6C>T)?

IFT172 p.His2= (c.6C>T) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

c.6C>T · rs1430470069 · VCV1113835

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00416%, nfe)

Conditions

short-rib thoracic dysplasia 10 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP 0.4, phastCons 0.21
Overall
CADD	11.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00416% European (non-Finnish) · 49/1,178,684 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00287%

Overall 0.0031% 50/1,612,086 alleles · very rare exomes 46/1,459,866 · genomes 4/152,220 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00416%	24,055
African / African-American	0.00134%	74,898

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: IFT172
Protein: p.His2=
Coding: c.6C>T
MANE Select: NM_015662
dbSNP: rs1430470069
Type: single nucleotide variant
Location: chr2:27489648 (GRCh38)
Gene constraint: LOEUF 0.745 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.98 · 1 PDB

Full IFT172 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 10 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 71

Similar variants

IFT172 p.His2Arg Uncertain significance ★ ⚠ same residue
IFT172 p.His2Pro Uncertain significance ★ ⚠ same residue
IFT172 p.His2Asn Uncertain significance ★★ ⚠ same residue
IFT172 c.1411+2T>C Likely pathogenic ★★ same condition
IFT172 c.1525-1G>A Pathogenic/Likely pathogenic ★★ same condition
IFT172 c.184-2A>C Likely pathogenic ★★ same condition
IFT172 c.2443-1G>C Likely pathogenic ★★ same condition
IFT172 c.2976-2A>T 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/ift172-p-his2 (accessed [today's date]).

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