Is APOL4 p.Val13Met (c.37G>A) pathogenic?

APOL4 p.Val13Met (c.37G>A) is classified Likely benign in APOL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-14). AlphaMissense: ambiguous (0.432); Ultra-rare (popmax 0.0493%, mid).

How common is APOL4 p.Val13Met (c.37G>A) in the general population?

APOL4 p.Val13Met (c.37G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about APOL4 p.Val13Met (c.37G>A)?

AlphaMissense predicts ambiguous (score 0.432) — an in-silico prediction, not a clinical call.

APOL4 p.Val13Met

c.37G>A · rs201355750 · VCV2595123

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.432 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.432	ambiguous
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -1.8
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.67 · regional, not allelic
Overall
CADD	5.586	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V16M vs ClinVar V13M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00551% 89/1,613,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Admixed American	0.0133%	7,501
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)	0.0061%	16,388
African / African-American	0.00267%	37,463

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: APOL4
Protein: p.Val13Met
Coding: c.37G>A
MANE Select: NM_001386885
dbSNP: rs201355750
Type: single nucleotide variant
Location: chr22:36199375 (GRCh38)
Gene constraint: LOEUF 1.863 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.08

Full APOL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOL4 c.-3G>A Uncertain significance ★ same type
APOL4 p.Ala5Gly Uncertain significance ★ ⚠ same type
APOL4 p.Ala5Pro Uncertain significance ★ ⚠ same type
APOL4 p.Arg31His Uncertain significance ★ ⚠ same type
APOL4 p.Asp301Glu Uncertain significance ★ ⚠ same type
APOL4 p.Gly24Glu Uncertain significance ★ ⚠ same type
APOL4 p.His17Arg Uncertain significance ★ ⚠ same type
APOL4 p.Ile14Asn 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/apol4-p-val13met (accessed [today's date]).

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