Is STRAP p.Ser23Asn (c.68G>A) pathogenic?

STRAP p.Ser23Asn (c.68G>A) is classified Uncertain significance in STRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely pathogenic (0.9922); Very rare (popmax 0.00551%, nfe).

How common is STRAP p.Ser23Asn (c.68G>A) in the general population?

STRAP p.Ser23Asn (c.68G>A) is very rare (popmax 0.00551%, nfe) (gnomAD).

What do computational predictors say about STRAP p.Ser23Asn (c.68G>A)?

AlphaMissense predicts likely pathogenic (score 0.9922) — an in-silico prediction, not a clinical call.

STRAP p.Ser23Asn

c.68G>A · VCV3450846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9922	likely pathogenic
REVEL	0.58	indeterminate
SaProt	LLR -14.18	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 90 bp · p 0.19 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00551% European (non-Finnish) · 65/1,180,000 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00403%

Overall 0.00421% 68/1,613,716 alleles · very rare exomes 66/1,461,480 · genomes 2/152,236 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00551%	18,154
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00133%	74,946

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: STRAP
Protein: p.Ser23Asn
Coding: c.68G>A
MANE Select: NM_007178
Type: single nucleotide variant
Location: chr12:15882775 (GRCh38)
Gene constraint: LOEUF 0.567 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 89.75

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

Similar variants

STRAP p.Ser23Gly Uncertain significance ★ ⚠ same residue
STRAP p.Ala149Val Uncertain significance ★ ⚠ same type
STRAP p.Ala211Val Uncertain significance ★ ⚠ same type
STRAP p.Ala35Gly Uncertain significance ★ ⚠ same type
STRAP p.Arg125Cys Uncertain significance ★ ⚠ same type
STRAP p.Asp163Glu Uncertain significance ★ ⚠ same type
STRAP p.Glu331Asp Uncertain significance ★ ⚠ same type
STRAP p.Gly24Arg 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/strap-p-ser23asn (accessed [today's date]).

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