Is IFNAR2 p.Phe8Ser (c.23T>C) pathogenic?

IFNAR2 p.Phe8Ser (c.23T>C) is classified Benign/Likely benign in IFNAR2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0849); Common (popmax 14.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency 45.

What condition is associated with IFNAR2 p.Phe8Ser (c.23T>C)?

IFNAR2 p.Phe8Ser (c.23T>C) is associated with immunodeficiency 45, hepatitis B virus, susceptibility to (ClinVar).

What do computational predictors say about IFNAR2 p.Phe8Ser (c.23T>C)?

AlphaMissense predicts likely benign (score 0.0849) — an in-silico prediction, not a clinical call.

IFNAR2 p.Phe8Ser

Q: How common is IFNAR2 p.Phe8Ser (c.23T>C) in the general population?

IFNAR2 p.Phe8Ser (c.23T>C) is common (popmax 14.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.23T>C · rs2229207 · VCV7288

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0849 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 14.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 45

Computational evidence

Protein change
AlphaMissense	0.0849	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.8	GERP -2.7
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.36 · regional, not allelic
Overall
CADD	0.756	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

Grpmax group 14.9% East Asian · 6,641/44,642 alleles

Filtering AF 14.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.5%

Overall 8.34% 134,141/1,608,462 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	14.9%	7
Admixed American	14.7%	7
South Asian	12.5%	8
Middle Eastern	11.9%	8
Remaining individualsnot grpmax-eligible	9.25%	11
Finnishnot grpmax-eligible	8.49%	12
African / African-American	8%	13
Ashkenazi Jewishnot grpmax-eligible	7.75%	13
European (non-Finnish)	7.42%	13
Amishnot grpmax-eligible	4.82%	21

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: IFNAR2
Protein: p.Phe8Ser
Coding: c.23T>C
dbSNP: rs2229207
Type: single nucleotide variant
Location: chr21:33241945 (GRCh38)

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

Disease context

immunodeficiency 45 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hepatitis B virus, susceptibility to

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-phe8ser (accessed [today's date]).

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