Is APOL6 p.Ala97Asp (c.290C>A) pathogenic?

APOL6 p.Ala97Asp (c.290C>A) is classified Uncertain significance in APOL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely pathogenic (0.8313); Very rare (popmax 0.00329%, sas).

How common is APOL6 p.Ala97Asp (c.290C>A) in the general population?

APOL6 p.Ala97Asp (c.290C>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about APOL6 p.Ala97Asp (c.290C>A)?

AlphaMissense predicts likely pathogenic (score 0.8313) — an in-silico prediction, not a clinical call.

APOL6 p.Ala97Asp

c.290C>A · VCV3935114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8313 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8313	likely pathogenic · top 1% in APOL6
REVEL	0.197	benign-leaning
SaProt	LLR -14.84	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -3.5
Regional constraint	o/e 1.02	unconstrained · MANE · 3,167 bp · p 0.67 · regional, not allelic
Overall
CADD	16.01	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 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000558% 9/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
African / African-American	0.00133%	74,908
European (non-Finnish)	0.000424%	236,007

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: APOL6
Protein: p.Ala97Asp
Coding: c.290C>A
MANE Select: NM_030641
Type: single nucleotide variant
Location: chr22:35658854 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI 0.16 (gnomAD)
Structure: AlphaFold pLDDT 54.86

Full APOL6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOL6 p.Ala161Val Uncertain significance ★ ⚠ same type
APOL6 p.Ala166Pro Uncertain significance ★ ⚠ same type
APOL6 p.Ala181Asp Uncertain significance ★ ⚠ same type
APOL6 p.Ala200Val Uncertain significance ★ ⚠ same type
APOL6 p.Ala263Thr Uncertain significance ★ ⚠ same type
APOL6 p.Ala275Asp Uncertain significance ★ ⚠ same type
APOL6 p.Ala300Ser Uncertain significance ★ ⚠ same type
APOL6 p.Ala5Val 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/apol6-p-ala97asp (accessed [today's date]).

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