Is IL7R p.Pro209Ser (c.625C>T) pathogenic?

IL7R p.Pro209Ser (c.625C>T) is classified Uncertain significance in IL7R (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-19). AlphaMissense: likely pathogenic (0.9527); Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with IL7R p.Pro209Ser (c.625C>T)?

IL7R p.Pro209Ser (c.625C>T) is associated with Inborn genetic diseases, immunodeficiency 104 (ClinVar).

How common is IL7R p.Pro209Ser (c.625C>T) in the general population?

IL7R p.Pro209Ser (c.625C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about IL7R p.Pro209Ser (c.625C>T)?

AlphaMissense predicts likely pathogenic (score 0.9527) — an in-silico prediction, not a clinical call.

IL7R p.Pro209Ser

c.625C>T · rs748643880 · VCV1470697

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9527 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9527	likely pathogenic · top 4% in IL7R
REVEL	0.458	indeterminate
SaProt	LLR -9.77	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 4.8	GERP 3.9, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 20 kb · p 2.2e-05 · regional, not allelic
Overall
CADD	23.5	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 0.0117% Admixed American · 7/59,996 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00062% 10/1,613,688 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,571
Remaining individualsnot grpmax-eligible	0.0016%	62,474
African / African-American	0.00134%	74,904
European (non-Finnish)	8.48e-05%	1,179,720

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.Pro209Ser
Coding: c.625C>T
MANE Select: NM_002185
dbSNP: rs748643880
Type: single nucleotide variant
Location: chr5:35873567 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.52 · 8 PDB
Residue 209: the fibronectin type-iii domain; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: immunodeficiency 104

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-pro209ser (accessed [today's date]).

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