Is AGTRAP p.Ser27= (c.81A>G) pathogenic?

AGTRAP p.Ser27= (c.81A>G) is classified Likely benign in AGTRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). Very rare (popmax 0.00119%, nfe).

How common is AGTRAP p.Ser27= (c.81A>G) in the general population?

AGTRAP p.Ser27= (c.81A>G) is very rare (popmax 0.00119%, nfe) (gnomAD).

AGTRAP p.Ser27=

c.81A>G · VCV4025473

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.012	strongly benign-leaning
Splicing
SpliceAI	Δ0.88	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -3.3	GERP -2.3
Overall
CADD	0.572	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,826 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000868% 14/1,613,786 alleles · very rare

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: AGTRAP
Protein: p.Ser27=
Coding: c.81A>G
MANE Select: NM_020350
Type: single nucleotide variant
Location: chr1:11747458 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 80.97

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

Similar variants

AGTRAP p.Arg157Gln Likely benign ★★ same type
AGTRAP p.Ala53Thr Uncertain significance ★ ⚠ same type
AGTRAP p.Arg113Cys Uncertain significance ★ ⚠ same type
AGTRAP p.Arg113His Uncertain significance ★ ⚠ same type
AGTRAP p.Arg130Cys Uncertain significance ★ ⚠ same type
AGTRAP p.Arg130Ser Uncertain significance ★ ⚠ same type
AGTRAP p.Arg157Leu Uncertain significance ★ ⚠ same type
AGTRAP p.Arg48Gln 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/agtrap-p-ser27 (accessed [today's date]).

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