Is IFT27 p.Pro50Thr (c.148C>A) pathogenic?

IFT27 p.Pro50Thr (c.148C>A) is classified Uncertain significance in IFT27 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). AlphaMissense: likely benign (0.0999); Very rare (popmax 0.00167%, amr).

How common is IFT27 p.Pro50Thr (c.148C>A) in the general population?

IFT27 p.Pro50Thr (c.148C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about IFT27 p.Pro50Thr (c.148C>A)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

IFT27 p.Pro50Thr

c.148C>A · rs2145920470 · VCV1353562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.13 · regional, not allelic
Overall
CADD	16.19	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

Grpmax group 0.00167% Admixed American · 1/59,996 alleles

Overall 6.2e-05% 1/1,613,752 alleles · very rare exomes 1/1,461,556 · genomes 0/152,196 · 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.Pro50Thr
Coding: c.148C>A
MANE Select: NM_001177701
dbSNP: rs2145920470
Type: single nucleotide variant
Location: chr22:36767332 (GRCh38)
Gene constraint: LOEUF 1.078 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.65

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

Similar variants

IFT27 p.Tyr36Cys Pathogenic ★★ same type
IFT27 c.114+5G>T Uncertain significance ★★ same type
IFT27 p.Arg26Cys Uncertain significance ★★ ⚠ same type
IFT27 p.Arg26His Uncertain significance ★★ ⚠ same type
IFT27 p.Leu44Phe Uncertain significance ★★ same type
IFT27 p.Lys3Gln Uncertain significance ★★ ⚠ same type
IFT27 c.114+8G>A Likely benign ★★ same type
IFT27 c.174+17C>T Likely benign ★★ same type

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-pro50thr (accessed [today's date]).

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