Is APOBR p.Ala196Val (c.587C>T) pathogenic?

APOBR p.Ala196Val (c.587C>T) is classified Likely benign in APOBR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: likely benign (0.0804); Very rare (popmax 0.00474%, sas).

How common is APOBR p.Ala196Val (c.587C>T) in the general population?

APOBR p.Ala196Val (c.587C>T) is very rare (popmax 0.00474%, sas) (gnomAD).

What do computational predictors say about APOBR p.Ala196Val (c.587C>T)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

APOBR p.Ala196Val

c.587C>T · VCV3934454

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00474%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.80	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 -6.1	GERP -3
Regional constraint	o/e 1.03	unconstrained · MANE · 3,820 bp · p 0.27 · regional, not allelic
Overall
CADD	0.121	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 0.00474% South Asian · 4/84,362 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000946%

Overall 0.000707% 11/1,556,500 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00474%	21,091
Remaining individualsnot grpmax-eligible	0.00331%	30,232
European (non-Finnish)	0.000435%	229,987

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: APOBR
Protein: p.Ala196Val
Coding: c.587C>T
MANE Select: NM_018690
Type: single nucleotide variant
Location: chr16:28495628 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 41.14
Residue 196: the 'disordered' region

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

Similar variants

APOBR p.Gln807Pro Benign ★★ same type
APOBR p.Gly350= Likely benign ★★ same type
APOBR p.Ala241Gly Uncertain significance ★ ⚠ same type
APOBR p.Ala283Val Uncertain significance ★ ⚠ same type
APOBR p.Ala292Val Uncertain significance ★ ⚠ same type
APOBR p.Ala301Thr Uncertain significance ★ ⚠ same type
APOBR p.Ala33Val Uncertain significance ★ ⚠ same type
APOBR p.Ala514Asp 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/apobr-p-ala196val (accessed [today's date]).

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