Is ABRAXAS2 p.Pro305Ser (c.913C>T) pathogenic?

ABRAXAS2 p.Pro305Ser (c.913C>T) is classified Uncertain significance in ABRAXAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.2219); Ultra-rare (popmax 0.0164%, mid).

How common is ABRAXAS2 p.Pro305Ser (c.913C>T) in the general population?

ABRAXAS2 p.Pro305Ser (c.913C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ABRAXAS2 p.Pro305Ser (c.913C>T)?

AlphaMissense predicts likely benign (score 0.2219) — an in-silico prediction, not a clinical call.

ABRAXAS2 p.Pro305Ser

c.913C>T · rs374500362 · VCV2458327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2219 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2219	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -10.00	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 6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,612 bp · p 0.65 · regional, not allelic
Overall
CADD	25.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0115%

Overall 0.0112% 180/1,613,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0208%	4,807
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.0139%	7,195
Admixed American	0.00167%	59,984
African / African-American	0.00134%	74,904

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABRAXAS2
Protein: p.Pro305Ser
Coding: c.913C>T
MANE Select: NM_032182
dbSNP: rs374500362
Type: single nucleotide variant
Location: chr10:124834636 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 4 PDB
Residue 305: the 'disordered' region

Full ABRAXAS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABRAXAS2 p.Ala161Asp Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala161Ser Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala208Thr Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala208Val Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala301Ser Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala3Val Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala72Thr Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Arg268Lys 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/abraxas2-p-pro305ser (accessed [today's date]).

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