Is IFNAR1 p.Ser173Phe (c.518C>T) pathogenic?

IFNAR1 p.Ser173Phe (c.518C>T) is classified Uncertain significance in IFNAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely benign (0.1779); Absent from gnomAD v4.1.

How common is IFNAR1 p.Ser173Phe (c.518C>T) in the general population?

IFNAR1 p.Ser173Phe (c.518C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFNAR1 p.Ser173Phe (c.518C>T)?

AlphaMissense predicts likely benign (score 0.1779) — an in-silico prediction, not a clinical call.

IFNAR1 p.Ser173Phe

c.518C>T · rs1445005547 · VCV1967049

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1779 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1779	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.32	donor loss · deltas
Pangolin	Δ0.24	loss · gain 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3	GERP 4.8, phastCons 0.14
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.52 · regional, not allelic
Overall
CADD	24.0	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

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: IFNAR1
Protein: p.Ser173Phe
Coding: c.518C>T
MANE Select: NM_000629
dbSNP: rs1445005547
Type: single nucleotide variant
Location: chr21:33343409 (GRCh38)
Gene constraint: LOEUF 1.73 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.71 · 5 PDB
Residue 173: the fibronectin type-iii 2 domain; a turn

Full IFNAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFNAR1 p.Ser173Cys Uncertain significance ★★ ⚠ same residue
IFNAR1 c.377-2A>G Likely pathogenic ★★ same type
IFNAR1 p.Tyr250Ter Pathogenic/Likely pathogenic ★★ same type
IFNAR1 p.Ala17Val Uncertain significance ★★ ⚠ same type
IFNAR1 p.Ala408Val Uncertain significance ★★ ⚠ same type
IFNAR1 p.Arg124His Uncertain significance ★★ ⚠ same type
IFNAR1 p.Arg306His Uncertain significance ★★ ⚠ same type
IFNAR1 p.Arg340Gly 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/ifnar1-p-ser173phe (accessed [today's date]).

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