Is AGTRAP p.Arg48Trp (c.142C>T) pathogenic?

AGTRAP p.Arg48Trp (c.142C>T) is classified Uncertain significance in AGTRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). AlphaMissense: likely benign (0.2612); Rare (popmax 0.127%, afr).

How common is AGTRAP p.Arg48Trp (c.142C>T) in the general population?

AGTRAP p.Arg48Trp (c.142C>T) is rare (popmax 0.127%, afr) (gnomAD).

What do computational predictors say about AGTRAP p.Arg48Trp (c.142C>T)?

AlphaMissense predicts likely benign (score 0.2612) — an in-silico prediction, not a clinical call.

AGTRAP p.Arg48Trp

c.142C>T · rs200088833 · VCV2356169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2612 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.127%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2612	likely benign
REVEL	0.427	indeterminate
SaProt	LLR -9.25	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.63	GERP 0.018, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.071 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.127% African / African-American · 95/75,040 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0983%

Overall 0.00688% 111/1,614,044 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.127%	790
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Admixed American	0.00333%	30,009
East Asian	0.00223%	44,886
European (non-Finnish)	0.000847%	117,998

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.Arg48Trp
Coding: c.142C>T
MANE Select: NM_020350
dbSNP: rs200088833
Type: single nucleotide variant
Location: chr1:11747519 (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.Arg48Gln 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-arg48trp (accessed [today's date]).

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