Is SHANK1 p.Asp508= (c.1524C>T) pathogenic?

SHANK1 p.Asp508= (c.1524C>T) is classified Likely benign in SHANK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-28). Rare (popmax 0.106%, afr); Associated with SHANK1-related disorder.

What condition is associated with SHANK1 p.Asp508= (c.1524C>T)?

SHANK1 p.Asp508= (c.1524C>T) is associated with SHANK1-related disorder (ClinVar).

How common is SHANK1 p.Asp508= (c.1524C>T) in the general population?

SHANK1 p.Asp508= (c.1524C>T) is rare (popmax 0.106%, afr) (gnomAD).

SHANK1 p.Asp508=

c.1524C>T · rs370465457 · VCV3047014

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.106%, afr)

Conditions

SHANK1-related disorder

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 -1.8	GERP -4.4
Overall
CADD	6.413	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.106% African / African-American · 78/73,614 alleles

Filtering AF 0.087% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.08%

Overall 0.00776% 120/1,547,108 alleles · rare exomes 70/1,394,848 · genomes 50/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.106%	944
Remaining individualsnot grpmax-eligible	0.0249%	4,020
Admixed American	0.0134%	7,483
South Asian	0.0118%	8,466
European (non-Finnish)	0.000868%	115,222

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: SHANK1
Protein: p.Asp508=
Coding: c.1524C>T
MANE Select: NM_016148
dbSNP: rs370465457
Type: single nucleotide variant
Location: chr19:50703529 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 48.59 · 7 PDB
Residue 508: the 'disordered' region

Full SHANK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SHANK1-related disorder

Similar variants

SHANK1 p.Arg1048Ter Pathogenic/Likely pathogenic ★★ same condition
SHANK1 p.Arg717Ter Pathogenic/Likely pathogenic ★★ same condition
SHANK1 p.Arg245Trp Likely pathogenic ★ same condition
SHANK1 p.Ala1652Pro Uncertain significance ★ ⚠ same condition
SHANK1 p.Gly1456Glu Uncertain significance ★ ⚠ same condition
SHANK1 p.Lys373Arg Uncertain significance ★ ⚠ same condition
SHANK1 p.Pro1467Arg Uncertain significance ★ ⚠ same condition
SHANK1 p.Arg197Trp Uncertain significance ⚠ 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/shank1-p-asp508 (accessed [today's date]).

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