Is SHANK1 p.Pro1815= (c.5445G>A) pathogenic?

SHANK1 p.Pro1815= (c.5445G>A) is classified Likely benign in SHANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-16). Very rare (popmax 0.00227%, sas).

How common is SHANK1 p.Pro1815= (c.5445G>A) in the general population?

SHANK1 p.Pro1815= (c.5445G>A) is very rare (popmax 0.00227%, sas) (gnomAD).

SHANK1 p.Pro1815=

c.5445G>A · rs928518446 · VCV739633

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00227%, sas)

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 -15	GERP -3
Overall
CADD	0.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00227% South Asian · 2/88,268 alleles

Filtering AF 0.000505% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000369%

Overall 0.00101% 16/1,583,488 alleles · very rare exomes 15/1,431,260 · genomes 1/152,228 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00326%	30,690
South Asiangrpmax	0.00227%	44,134
African / African-American	0.00134%	74,578
European (non-Finnish)	0.000942%	106,174

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1815=
Coding: c.5445G>A
MANE Select: NM_016148
dbSNP: rs928518446
Type: single nucleotide variant
Location: chr19:50666515 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 48.59 · 7 PDB

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

Similar variants

SHANK1 p.Pro1815Leu Likely benign ★ same residue
SHANK1 p.Pro1815fs Uncertain significance ★ same residue
SHANK1 p.Arg1048Ter Pathogenic/Likely pathogenic ★★ same type
SHANK1 p.Arg713Ter Pathogenic ★★ same type
SHANK1 p.Arg717Ter Pathogenic/Likely pathogenic ★★ same type
SHANK1 p.Ala893Val Uncertain significance ★★ ⚠ same type
SHANK1 p.Arg1423Gly Uncertain significance ★★ ⚠ same type
SHANK1 p.Arg2153Gln 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/shank1-p-pro1815 (accessed [today's date]).

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