Is IFNAR2 p.Phe10Val (c.28T>G) pathogenic?

IFNAR2 p.Phe10Val (c.28T>G) is classified Benign/Likely benign in IFNAR2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0451); Common (popmax 56.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency 45.

What condition is associated with IFNAR2 p.Phe10Val (c.28T>G)?

IFNAR2 p.Phe10Val (c.28T>G) is associated with immunodeficiency 45 (ClinVar).

What do computational predictors say about IFNAR2 p.Phe10Val (c.28T>G)?

AlphaMissense predicts likely benign (score 0.0451) — an in-silico prediction, not a clinical call.

IFNAR2 p.Phe10Val

Q: How common is IFNAR2 p.Phe10Val (c.28T>G) in the general population?

IFNAR2 p.Phe10Val (c.28T>G) is common (popmax 56.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.28T>G · rs1051393 · VCV1170800

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0451 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 56.7%, 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	0.0451	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -7
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.36 · regional, not allelic
Overall
CADD	0.008	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 56.7% East Asian · 25,310/44,640 alleles

Filtering AF 56.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 55.9%

Overall 33.5% 538,331/1,606,830 alleles · common exomes 490,087/1,454,762 · genomes 48,244/152,068 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	56.7%	2
South Asian	47.1%	2
Admixed American	44.9%	2
Middle Eastern	39.4%	3
Finnishnot grpmax-eligible	38.8%	3
Remaining individualsnot grpmax-eligible	34.7%	3
Ashkenazi Jewishnot grpmax-eligible	32.1%	3
European (non-Finnish)	31.6%	3
Amishnot grpmax-eligible	24.5%	4
African / African-American	19.5%	5

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.Phe10Val
Coding: c.28T>G
MANE Select: NM_001289125
dbSNP: rs1051393
Type: single nucleotide variant
Location: chr21:33241950 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.86 · 9 PDB
Residue 10: a UniProt-annotated variant site (in)

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

Similar variants

IFNAR2 p.Phe10Ile Uncertain significance ⚠ same residue
IFNAR2 c.840+1G>T Uncertain significance ★★ same condition
IFNAR2 p.Glu356Gly Uncertain significance ★★ ⚠ same condition
IFNAR2 c.541-50A>G Benign ★★ same condition
IFNAR2 c.841-102G>A Uncertain significance ★ same condition
IFNAR2 p.Gly115Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
IFNAR2 p.Ser53Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
IFNAR2 p.Val169Ile Conflicting classifications of pathogenicity ★ ⚠ same condition

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-phe10val (accessed [today's date]).

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