Is IFT172 p.Gly1069Arg (c.3205G>A) pathogenic?

IFT172 p.Gly1069Arg (c.3205G>A) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: ambiguous (0.3763); Absent from gnomAD v4.1; Associated with short-rib thoracic dysplasia 10 with or without polydactyly.

What condition is associated with IFT172 p.Gly1069Arg (c.3205G>A)?

IFT172 p.Gly1069Arg (c.3205G>A) is associated with short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

How common is IFT172 p.Gly1069Arg (c.3205G>A) in the general population?

IFT172 p.Gly1069Arg (c.3205G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT172 p.Gly1069Arg (c.3205G>A)?

AlphaMissense predicts ambiguous (score 0.3763) — an in-silico prediction, not a clinical call.

IFT172 p.Gly1069Arg

c.3205G>A · rs1666267219 · VCV1047310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

short-rib thoracic dysplasia 10 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.3763	ambiguous
REVEL	0.117	moderately benign-leaning
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,831 bp · p 1.1e-06 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IFT172
Protein: p.Gly1069Arg
Coding: c.3205G>A
MANE Select: NM_015662
dbSNP: rs1666267219
Type: single nucleotide variant
Location: chr2:27457662 (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.Gly1069Glu 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
IFT172 c.3111+1G>T Likely pathogenic ★★ same condition
IFT172 c.3821+1G>A 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/ift172-p-gly1069arg (accessed [today's date]).

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