Is TYROBP p.Pro110Leu (c.329C>T) pathogenic?

TYROBP p.Pro110Leu (c.329C>T) is classified Likely benign in TYROBP (ClinVar, No assertion criteria, 2 submitters). AlphaMissense: likely benign (0.2587); Ultra-rare (popmax 0.0134%, eas).

How common is TYROBP p.Pro110Leu (c.329C>T) in the general population?

TYROBP p.Pro110Leu (c.329C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about TYROBP p.Pro110Leu (c.329C>T)?

AlphaMissense predicts likely benign (score 0.2587) — an in-silico prediction, not a clinical call.

TYROBP p.Pro110Leu

c.329C>T · rs775997204 · VCV1205974

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2587 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2587	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -7.78	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 -0.018	GERP -3.4, phastCons 0.003
Regional constraint	o/e 1.06	unconstrained · MANE · 3,656 bp · p 0.43 · regional, not allelic
Overall
CADD	12.25	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 0.0134% East Asian · 6/44,888 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000744% 12/1,613,398 alleles · ultra-rare exomes 11/1,461,472 · genomes 1/151,926 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,481
Remaining individualsnot grpmax-eligible	0.0032%	31,235
South Asian	0.0022%	45,453
Admixed American	0.00167%	59,906
European (non-Finnish)	8.48e-05%	1,179,871

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: TYROBP
Protein: p.Pro110Leu
Coding: c.329C>T
MANE Select: NM_003332
dbSNP: rs775997204
Type: single nucleotide variant
Location: chr19:35904582 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.10 · 5 PDB
Residue 110: the 'disordered' region

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

Similar variants

TYROBP p.Pro110= Likely benign ★ same residue
TYROBP p.Ala44Thr Uncertain significance ★★ ⚠ same type
TYROBP p.Arg70Trp Uncertain significance ★★ ⚠ same type
TYROBP p.Asp104Asn Uncertain significance ★★ ⚠ same type
TYROBP p.Asp32Asn Uncertain significance ★★ ⚠ same type
TYROBP p.Pro40Leu Uncertain significance ★★ same type
TYROBP p.Ser99Leu Uncertain significance ★★ ⚠ same type
TYROBP p.Val38Met 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/tyrobp-p-pro110leu (accessed [today's date]).

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