Is IFT172 p.Ala554Ser (c.1660G>T) pathogenic?

IFT172 p.Ala554Ser (c.1660G>T) is classified Uncertain significance in IFT172 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-09). AlphaMissense: likely benign (0.0812); Absent from gnomAD v4.1; Associated with IFT172-related disorder.

What condition is associated with IFT172 p.Ala554Ser (c.1660G>T)?

IFT172 p.Ala554Ser (c.1660G>T) is associated with IFT172-related disorder (ClinVar).

How common is IFT172 p.Ala554Ser (c.1660G>T) in the general population?

IFT172 p.Ala554Ser (c.1660G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT172 p.Ala554Ser (c.1660G>T)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

IFT172 p.Ala554Ser

c.1660G>T · rs2465943447 · VCV2629947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

IFT172-related disorder

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -3.14	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 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.013 · regional, not allelic
Overall
CADD	18.82	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

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.Ala554Ser
Coding: c.1660G>T
MANE Select: NM_015662
dbSNP: rs2465943447
Type: single nucleotide variant
Location: chr2:27470960 (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

IFT172-related disorder

Similar variants

IFT172 p.Ala554Thr Uncertain significance ★ ⚠ same residue
IFT172 p.Ala554= Likely benign ★ same residue
IFT172 c.1525-1G>A Pathogenic/Likely pathogenic ★★ same condition
IFT172 c.184-2A>C Likely pathogenic ★★ same condition
IFT172 c.786-2A>G Likely pathogenic ★★ same condition
IFT172 p.Arg346Ter Pathogenic/Likely pathogenic ★★ same condition
IFT172 p.Arg38Ter Pathogenic/Likely pathogenic ★★ same condition
IFT172 p.Arg685Ter 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-ala554ser (accessed [today's date]).

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