Is IFT27 p.Pro82Leu (c.245C>T) pathogenic?

IFT27 p.Pro82Leu (c.245C>T) is classified Uncertain significance in IFT27 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-03-22). AlphaMissense: likely pathogenic (0.6647); Very rare (popmax 0.00891%, nfe); Associated with Inborn genetic diseases.

What condition is associated with IFT27 p.Pro82Leu (c.245C>T)?

IFT27 p.Pro82Leu (c.245C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IFT27 p.Pro82Leu (c.245C>T) in the general population?

IFT27 p.Pro82Leu (c.245C>T) is very rare (popmax 0.00891%, nfe) (gnomAD).

What do computational predictors say about IFT27 p.Pro82Leu (c.245C>T)?

AlphaMissense predicts likely pathogenic (score 0.6647) — an in-silico prediction, not a clinical call.

IFT27 p.Pro82Leu

c.245C>T · rs140877667 · VCV1026719

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6647 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, nfe)

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	0.6647	likely pathogenic
REVEL	0.61	indeterminate
SaProt	LLR -12.44	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 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.13 · regional, not allelic
Overall
CADD	27.5	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 0.00891% European (non-Finnish) · 105/1,177,882 alleles

Filtering AF 0.0075% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00702%

Overall 0.00664% 107/1,611,736 alleles · very rare exomes 98/1,459,530 · genomes 9/152,206 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00891%	11,218
African / African-American	0.00267%	37,440

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.Pro82Leu
Coding: c.245C>T
MANE Select: NM_001177701
dbSNP: rs140877667
Type: single nucleotide variant
Location: chr22:36764026 (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-pro82leu (accessed [today's date]).

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