Is ABI3 p.Ser91Arg (c.271A>C) pathogenic?

ABI3 p.Ser91Arg (c.271A>C) is classified Uncertain significance in ABI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: ambiguous (0.4333); Very rare (popmax 0.00804%, sas).

How common is ABI3 p.Ser91Arg (c.271A>C) in the general population?

ABI3 p.Ser91Arg (c.271A>C) is very rare (popmax 0.00804%, sas) (gnomAD).

What do computational predictors say about ABI3 p.Ser91Arg (c.271A>C)?

AlphaMissense predicts ambiguous (score 0.4333) — an in-silico prediction, not a clinical call.

ABI3 p.Ser91Arg

c.271A>C · VCV3993349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00804%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4333	ambiguous
REVEL	0.21	benign-leaning
SaProt	LLR -9.90	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.64	donor loss, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 12 kb · p 0.85 · regional, not allelic
Overall
CADD	22.5	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 0.00804% South Asian · 7/87,096 alleles

Filtering AF 0.00373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00264%

Overall 0.00049% 7/1,428,796 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: ABI3
Protein: p.Ser91Arg
Coding: c.271A>C
MANE Select: NM_016428
Type: single nucleotide variant
Location: chr17:49216684 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.31

Full ABI3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABI3 p.Glu87= Benign ★★ same type
ABI3 p.Pro174= Benign ★★ same type
ABI3 p.Ala126Ser Uncertain significance ★ ⚠ same type
ABI3 p.Ala173Gly Uncertain significance ★ ⚠ same type
ABI3 p.Ala173Ser Uncertain significance ★ ⚠ same type
ABI3 p.Ala178Thr Uncertain significance ★ ⚠ same type
ABI3 p.Ala18Thr Uncertain significance ★ ⚠ same type
ABI3 p.Ala204Val 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/abi3-p-ser91arg (accessed [today's date]).

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