Is AFAP1 p.Glu512Lys (c.1534G>A) pathogenic?

AFAP1 p.Glu512Lys (c.1534G>A) is classified Uncertain significance in AFAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). Very rare (popmax 0.00411%, afr).

How common is AFAP1 p.Glu512Lys (c.1534G>A) in the general population?

AFAP1 p.Glu512Lys (c.1534G>A) is very rare (popmax 0.00411%, afr) (gnomAD).

AFAP1 p.Glu512Lys

c.1534G>A · VCV3839656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00411%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 108 kb · p 3.6e-06 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00411% African / African-American · 3/73,036 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000502%

Overall 0.000193% 3/1,551,590 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: AFAP1
Protein: p.Glu512Lys
Coding: c.1534G>A
MANE Select: NM_001134647
Type: single nucleotide variant
Location: chr4:7781624 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.09
Residue 512: the 'disordered' region

Full AFAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AFAP1 p.Val288Ala Uncertain significance ★★ ⚠ same type
AFAP1 p.Ala783= Likely benign ★★ same type
AFAP1 p.Asn686= Likely benign ★★ same type
AFAP1 p.Glu705= Benign ★★ same type
AFAP1 p.Ala438Ser Uncertain significance ★ ⚠ same type
AFAP1 p.Ala534Ser Uncertain significance ★ same type
AFAP1 p.Ala587Val Uncertain significance ★ same type
AFAP1 p.Ala624Val 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/afap1-p-glu512lys (accessed [today's date]).

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