Is IFNAR2 p.Pro136Leu (c.407C>T) pathogenic?

IFNAR2 p.Pro136Leu (c.407C>T) is classified Uncertain significance in IFNAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: likely pathogenic (0.5829); Absent from gnomAD v4.1.

How common is IFNAR2 p.Pro136Leu (c.407C>T) in the general population?

IFNAR2 p.Pro136Leu (c.407C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFNAR2 p.Pro136Leu (c.407C>T)?

AlphaMissense predicts likely pathogenic (score 0.5829) — an in-silico prediction, not a clinical call.

IFNAR2 p.Pro136Leu

c.407C>T · rs768348126 · VCV2070100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5829 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5829	likely pathogenic
REVEL	0.388	indeterminate
SaProt	LLR -9.00	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 4.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.36 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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: IFNAR2
Protein: p.Pro136Leu
Coding: c.407C>T
MANE Select: NM_001289125
dbSNP: rs768348126
Type: single nucleotide variant
Location: chr21:33248721 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.86 · 9 PDB
Residue 136: an α-helix

Full IFNAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFNAR2 p.Pro136Ser Uncertain significance ★★ ⚠ same residue
IFNAR2 c.840+1G>T Uncertain significance ★★ same type
IFNAR2 p.Arg397Gly Uncertain significance ★★ ⚠ same type
IFNAR2 p.Arg90Gly Uncertain significance ★★ ⚠ same type
IFNAR2 p.Asn146Ser Uncertain significance ★★ ⚠ same type
IFNAR2 p.Asn281Tyr Uncertain significance ★★ ⚠ same type
IFNAR2 p.Asp198Gly Uncertain significance ★★ ⚠ same type
IFNAR2 p.Asp437Gly Uncertain significance ★★ ⚠ 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/ifnar2-p-pro136leu (accessed [today's date]).

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