Is IL7R p.Ser407= (c.1221C>T) pathogenic?

IL7R p.Ser407= (c.1221C>T) is classified Likely benign in IL7R (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-30). Very rare (popmax 0.0011%, sas); Associated with immunodeficiency 104.

What condition is associated with IL7R p.Ser407= (c.1221C>T)?

IL7R p.Ser407= (c.1221C>T) is associated with immunodeficiency 104 (ClinVar).

How common is IL7R p.Ser407= (c.1221C>T) in the general population?

IL7R p.Ser407= (c.1221C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

IL7R p.Ser407=

c.1221C>T · rs267600610 · VCV2748481

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

immunodeficiency 104

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.78	GERP -2.6
Overall
CADD	2.366	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,042 alleles

Overall 0.000137% 2/1,461,090 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,042
European (non-Finnish)	8.48e-05%	1,179,439

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: IL7R
Protein: p.Ser407=
Coding: c.1221C>T
MANE Select: NM_002185
dbSNP: rs267600610
Type: single nucleotide variant
Location: chr5:35876327 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.52 · 8 PDB

Full IL7R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 104 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IL7R c.221+1G>A Pathogenic ★★★ same condition
IL7R c.221+2T>G Pathogenic ★★★ same condition
IL7R c.537+1G>A Pathogenic ★★★ same condition
IL7R c.538-1G>A Pathogenic ★★★ same condition
IL7R c.83-2A>T Pathogenic ★★★ same condition
IL7R p.Arg206Ter Pathogenic ★★★ same condition
IL7R p.Cys118Tyr Pathogenic ★★★ same condition
IL7R p.Gln89Ter Likely pathogenic ★★★ 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/il7r-p-ser407 (accessed [today's date]).

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