Is IFT27 p.Pro163Ser (c.487C>T) pathogenic?

IFT27 p.Pro163Ser (c.487C>T) is classified Uncertain significance in IFT27 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.6305); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with IFT27 p.Pro163Ser (c.487C>T)?

IFT27 p.Pro163Ser (c.487C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IFT27 p.Pro163Ser (c.487C>T) in the general population?

IFT27 p.Pro163Ser (c.487C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about IFT27 p.Pro163Ser (c.487C>T)?

AlphaMissense predicts likely pathogenic (score 0.6305) — an in-silico prediction, not a clinical call.

IFT27 p.Pro163Ser

c.487C>T · rs1937988974 · VCV939760

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6305 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.6305	likely pathogenic
REVEL	0.63	indeterminate
SaProt	LLR -13.87	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.13 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.015% Admixed American · 9/59,998 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00062% 10/1,613,926 alleles · ultra-rare exomes 9/1,461,780 · genomes 1/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,666
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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: IFT27
Protein: p.Pro163Ser
Coding: c.487C>T
MANE Select: NM_001177701
dbSNP: rs1937988974
Type: single nucleotide variant
Location: chr22:36758385 (GRCh38)

Full IFT27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/ift27-p-pro163ser (accessed [today's date]).

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