Is TRAIP p.Arg157His (c.470G>A) pathogenic?

TRAIP p.Arg157His (c.470G>A) is classified Benign/Likely benign in TRAIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0824); Low-frequency (popmax 1.07%, eas).

How common is TRAIP p.Arg157His (c.470G>A) in the general population?

TRAIP p.Arg157His (c.470G>A) is low-frequency (popmax 1.07%, eas) (gnomAD).

What do computational predictors say about TRAIP p.Arg157His (c.470G>A)?

AlphaMissense predicts likely benign (score 0.0824) — an in-silico prediction, not a clinical call.

TRAIP p.Arg157His

c.470G>A · rs143366962 · VCV2159974

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0824 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0824	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP 0.55, phastCons 0.99
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	22.8	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 1.07% East Asian · 479/44,874 alleles

Filtering AF 0.988% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.957%

Overall 0.0327% 527/1,613,968 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.07%	94
Remaining individualsnot grpmax-eligible	0.0288%	3,473
European (non-Finnish)	0.00237%	42,142
South Asian	0.0022%	45,539

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: TRAIP
Protein: p.Arg157His
Coding: c.470G>A
MANE Select: NM_005879
dbSNP: rs143366962
Type: single nucleotide variant
Location: chr3:49842486 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB

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

Similar variants

TRAIP p.Arg157Gly Uncertain significance ★ ⚠ same residue
TRAIP p.Arg436Cys Uncertain significance ★★ ⚠ same type
TRAIP p.Arg436His Uncertain significance ★★ ⚠ same type
TRAIP p.Asp244His Uncertain significance ★★ ⚠ same type
TRAIP p.Asp431Gly Uncertain significance ★★ ⚠ same type
TRAIP p.Gln36Arg Uncertain significance ★★ ⚠ same type
TRAIP p.Glu209Lys Uncertain significance ★★ ⚠ same type
TRAIP p.Gly421Ser 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/traip-p-arg157his (accessed [today's date]).

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