Is SNRNP200 p.Ile1663Thr (c.4988T>C) pathogenic?

SNRNP200 p.Ile1663Thr (c.4988T>C) is classified Likely benign in SNRNP200 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely pathogenic (0.8403); Very rare (popmax 0.00133%, afr).

How common is SNRNP200 p.Ile1663Thr (c.4988T>C) in the general population?

SNRNP200 p.Ile1663Thr (c.4988T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about SNRNP200 p.Ile1663Thr (c.4988T>C)?

AlphaMissense predicts likely pathogenic (score 0.8403) — an in-silico prediction, not a clinical call.

SNRNP200 p.Ile1663Thr

c.4988T>C · rs145701974 · VCV837384

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8403 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8403	likely pathogenic
REVEL	0.926	moderately pathogenic-leaning
SaProt	LLR -13.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 11 kb · p 1.9e-29 · regional, not allelic
Overall
CADD	27.5	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 0.00133% African / African-American · 1/74,908 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,990 alleles · very rare exomes 4/1,461,824 · genomes 1/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,908
European (non-Finnish)	0.000339%	294,998

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: SNRNP200
Protein: p.Ile1663Thr
Coding: c.4988T>C
MANE Select: NM_014014
dbSNP: rs145701974
Type: single nucleotide variant
Location: chr2:96281850 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.89 · 85 PDB
Residue 1663: a β-strand; the helicase c-terminal 2 domain; the 'interaction with c9orf78 and wbp4' region; the 'interaction with tssc4' region

Full SNRNP200 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SNRNP200 p.Ile1663Val Conflicting classifications of pathogenicity ★ ⚠ same residue
SNRNP200 p.Ile1663del Uncertain significance ★ same residue
SNRNP200 p.Ala542Val Likely pathogenic ★★ same type
SNRNP200 p.Ala787Thr Pathogenic/Likely pathogenic ★★ same type
SNRNP200 p.Arg681Cys Pathogenic/Likely pathogenic ★★ same type
SNRNP200 p.Arg681His Pathogenic/Likely pathogenic ★★ same type
SNRNP200 p.Pro682Ser Pathogenic/Likely pathogenic ★★ same type
SNRNP200 p.Ser1087Leu Pathogenic ★★ 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/snrnp200-p-ile1663thr (accessed [today's date]).

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