Is SNIP1 p.Val28= (c.84G>A) pathogenic?

SNIP1 p.Val28= (c.84G>A) is classified Benign in SNIP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 42.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with psychomotor retardation, epilepsy, and craniofacial dysmorphism.

What condition is associated with SNIP1 p.Val28= (c.84G>A)?

SNIP1 p.Val28= (c.84G>A) is associated with psychomotor retardation, epilepsy, and craniofacial dysmorphism (ClinVar).

SNIP1 p.Val28=

Q: How common is SNIP1 p.Val28= (c.84G>A) in the general population?

SNIP1 p.Val28= (c.84G>A) is common (popmax 42.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.84G>A · rs2273013 · VCV1170158

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 42.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

psychomotor retardation, epilepsy, and craniofacial dysmorphism

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 0.72	GERP -1.1, phastCons 1
Overall
CADD	13.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.8% East Asian · 19,180/44,814 alleles

Filtering AF 42.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.1%

Overall 19.4% 313,403/1,612,118 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	42.8%	2
Admixed American	31.8%	3
South Asian	22.3%	4
Finnishnot grpmax-eligible	21.6%	5
Amishnot grpmax-eligible	20.2%	5
Remaining individualsnot grpmax-eligible	19.9%	5
Middle Eastern	18.8%	5
European (non-Finnish)	18.4%	5
Ashkenazi Jewishnot grpmax-eligible	17.3%	6
African / African-American	6.96%	14

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: SNIP1
Protein: p.Val28=
Coding: c.84G>A
MANE Select: NM_024700
dbSNP: rs2273013
Type: single nucleotide variant
Location: chr1:37554146 (GRCh38)
Gene constraint: LOEUF 0.865 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.66 · 10 PDB
Residue 28: the 'disordered' region

Full SNIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

psychomotor retardation, epilepsy, and craniofacial dysmorphism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SNIP1 p.Asp386Asn Uncertain significance ★★ ⚠ same condition
SNIP1 p.Leu352Val Uncertain significance ★★ ⚠ same condition
SNIP1 p.Asp113Tyr Uncertain significance ★ ⚠ same condition
SNIP1 p.Glu366Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
SNIP1 p.Phe362Tyr Uncertain significance ★ ⚠ same condition
SNIP1 p.Asp380fs Uncertain significance ★ same condition
SNIP1 p.Arg144Trp Uncertain significance ★★ ⚠ same type
SNIP1 p.Arg322Gln 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/snip1-p-val28 (accessed [today's date]).

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