Is AGTRAP p.Pro4Arg (c.11C>G) pathogenic?

AGTRAP p.Pro4Arg (c.11C>G) is classified Uncertain significance in AGTRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: ambiguous (0.3624); Ultra-rare (popmax 0.0139%, nfe).

How common is AGTRAP p.Pro4Arg (c.11C>G) in the general population?

AGTRAP p.Pro4Arg (c.11C>G) is ultra-rare (popmax 0.0139%, nfe) (gnomAD).

What do computational predictors say about AGTRAP p.Pro4Arg (c.11C>G)?

AlphaMissense predicts ambiguous (score 0.3624) — an in-silico prediction, not a clinical call.

AGTRAP p.Pro4Arg

c.11C>G · rs764597773 · VCV2348883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3624 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0139%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3624	ambiguous
REVEL	0.276	benign-leaning
SaProt	LLR -8.84	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.071 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0139% European (non-Finnish) · 164/1,177,938 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0115%

Overall 0.0104% 167/1,607,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0139%	7,183
Remaining individualsnot grpmax-eligible	0.00322%	31,096
African / African-American	0.00134%	74,882

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.Pro4Arg
Coding: c.11C>G
MANE Select: NM_020350
dbSNP: rs764597773
Type: single nucleotide variant
Location: chr1:11736219 (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.Pro4Ser Uncertain significance ★ ⚠ same residue
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

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-pro4arg (accessed [today's date]).

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