Is IFT172 p.Arg136Cys (c.406C>T) pathogenic?

IFT172 p.Arg136Cys (c.406C>T) is classified Uncertain significance in IFT172 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-04). AlphaMissense: likely pathogenic (0.8491); Ultra-rare (popmax 0.0201%, eas); Associated with retinitis pigmentosa 71.

What condition is associated with IFT172 p.Arg136Cys (c.406C>T)?

IFT172 p.Arg136Cys (c.406C>T) is associated with retinitis pigmentosa 71, short-rib thoracic dysplasia 10 with or without polydactyly, Bardet-Biedl syndrome 20 (ClinVar).

How common is IFT172 p.Arg136Cys (c.406C>T) in the general population?

IFT172 p.Arg136Cys (c.406C>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IFT172 p.Arg136Cys (c.406C>T)?

AlphaMissense predicts likely pathogenic (score 0.8491) — an in-silico prediction, not a clinical call.

IFT172 p.Arg136Cys

c.406C>T · rs753783467 · VCV1000290

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8491 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 71

Computational evidence

Protein change
AlphaMissense	0.8491	likely pathogenic
REVEL	0.733	pathogenic-leaning
SaProt	LLR -9.51	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,878 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000867% 14/1,613,882 alleles · ultra-rare exomes 14/1,461,696 · genomes 0/152,186 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,986
South Asian	0.0033%	30,345
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	8.47e-05%	1,179,942

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.Arg136Cys
Coding: c.406C>T
MANE Select: NM_015662
dbSNP: rs753783467
Type: single nucleotide variant
Location: chr2:27483656 (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

retinitis pigmentosa 71 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: short-rib thoracic dysplasia 10 with or without polydactyly Bardet-Biedl syndrome 20

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

IFT172 p.Arg136His Uncertain significance ★★ ⚠ same residue
IFT172 p.Arg136= Likely benign 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
IFT172 c.3111+1G>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-arg136cys (accessed [today's date]).

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