Is IFT172 p.Arg720His (c.2159G>A) pathogenic?

IFT172 p.Arg720His (c.2159G>A) is classified Conflicting classifications of pathogenicity in IFT172 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.0856); Ultra-rare (popmax 0.0124%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with IFT172 p.Arg720His (c.2159G>A)?

IFT172 p.Arg720His (c.2159G>A) is associated with inherited retinal dystrophy, short-rib thoracic dysplasia 10 with or without polydactyly, retinitis pigmentosa 71 (ClinVar).

How common is IFT172 p.Arg720His (c.2159G>A) in the general population?

IFT172 p.Arg720His (c.2159G>A) is ultra-rare (popmax 0.0124%, nfe) (gnomAD).

What do computational predictors say about IFT172 p.Arg720His (c.2159G>A)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

IFT172 p.Arg720His

c.2159G>A · rs202089120 · VCV964509

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -7.07	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 4	GERP 1.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	23.8	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 0.0124% European (non-Finnish) · 146/1,180,038 alleles

Filtering AF 0.0107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.01%

Overall 0.0107% 172/1,614,180 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0124%	8,082
Admixed American	0.0117%	8,574
African / African-American	0.0107%	9,380
Remaining individualsnot grpmax-eligible	0.008%	12,501
East Asian	0.00446%	22,442
South Asian	0.00329%	30,360
Finnishnot grpmax-eligible	0.00156%	64,038

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.Arg720His
Coding: c.2159G>A
MANE Select: NM_015662
dbSNP: rs202089120
Type: single nucleotide variant
Location: chr2:27461793 (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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: short-rib thoracic dysplasia 10 with or without polydactyly retinitis pigmentosa 71 Bardet-Biedl syndrome 20

Similar variants

IFT172 p.Arg720Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
IFT172 p.Arg720Pro Uncertain significance ★ ⚠ same residue
IFT172 p.Arg720fs Pathogenic/Likely pathogenic ★★ 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-arg720his (accessed [today's date]).

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