Is IL15 p.Ser77Arg (c.231T>G) pathogenic?

IL15 p.Ser77Arg (c.231T>G) is classified Uncertain significance in IL15 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: likely pathogenic (0.6699); Very rare (popmax 0.00583%, afr).

How common is IL15 p.Ser77Arg (c.231T>G) in the general population?

IL15 p.Ser77Arg (c.231T>G) is very rare (popmax 0.00583%, afr) (gnomAD).

What do computational predictors say about IL15 p.Ser77Arg (c.231T>G)?

AlphaMissense predicts likely pathogenic (score 0.6699) — an in-silico prediction, not a clinical call.

IL15 p.Ser77Arg

c.231T>G · rs779898572 · VCV2285563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6699 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00583%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6699	likely pathogenic
REVEL	0.249	benign-leaning
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.44 · regional, not allelic
Overall
CADD	21.2	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 0.00583% African / African-American · 4/68,558 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00112%

Overall 0.000295% 4/1,357,690 alleles · very rare exomes 1/1,205,568 · genomes 3/152,122 · joint denominator

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: IL15
Protein: p.Ser77Arg
Coding: c.231T>G
MANE Select: NM_000585
dbSNP: rs779898572
Type: single nucleotide variant
Location: chr4:141727975 (GRCh38)
Gene constraint: LOEUF 1.736 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.73 · 4 PDB

Full IL15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL15 p.Cys136= Likely benign ★★ same type
IL15 p.Leu117= Benign ★★ same type
IL15 p.Ala29Gly Uncertain significance ★ ⚠ same type
IL15 p.Asp78Glu Uncertain significance ★ ⚠ same type
IL15 p.Glu146Gln Uncertain significance ★ ⚠ same type
IL15 p.His32Arg Uncertain significance ★ ⚠ same type
IL15 p.His80Tyr Uncertain significance ★ ⚠ same type
IL15 p.Ile144Phe 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/il15-p-ser77arg (accessed [today's date]).

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