Is IFT27 p.Cys86Arg (c.256T>C) pathogenic?

IFT27 p.Cys86Arg (c.256T>C) is classified Uncertain significance in IFT27 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-11). AlphaMissense: likely pathogenic (0.9941); Very rare (popmax 8.48e-05%, nfe).

How common is IFT27 p.Cys86Arg (c.256T>C) in the general population?

IFT27 p.Cys86Arg (c.256T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about IFT27 p.Cys86Arg (c.256T>C)?

AlphaMissense predicts likely pathogenic (score 0.9941) — an in-silico prediction, not a clinical call.

IFT27 p.Cys86Arg

c.256T>C · rs2517823941 · VCV2005057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.9941	likely pathogenic
REVEL	0.862	moderately pathogenic-leaning
SaProt	LLR -14.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.13 · regional, not allelic
Overall
CADD	28.9	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 8.48e-05% European (non-Finnish) · 1/1,179,670 alleles

Overall 6.2e-05% 1/1,613,870 alleles · very rare exomes 1/1,461,482 · genomes 0/152,388 · joint denominator

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.Cys86Arg
Coding: c.256T>C
MANE Select: NM_001177701
dbSNP: rs2517823941
Type: single nucleotide variant
Location: chr22:36764015 (GRCh38)

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

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-cys86arg (accessed [today's date]).

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