Is ANKRD27 p.Ala522Val (c.1565C>T) pathogenic?

ANKRD27 p.Ala522Val (c.1565C>T) is classified Uncertain significance in ANKRD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.0831); Very rare (popmax 0.00619%, nfe).

How common is ANKRD27 p.Ala522Val (c.1565C>T) in the general population?

ANKRD27 p.Ala522Val (c.1565C>T) is very rare (popmax 0.00619%, nfe) (gnomAD).

What do computational predictors say about ANKRD27 p.Ala522Val (c.1565C>T)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

ANKRD27 p.Ala522Val

c.1565C>T · rs776736848 · VCV2391626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00619%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 61 kb · p 0.24 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00619% European (non-Finnish) · 73/1,179,132 alleles

Filtering AF 0.00503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00463%

Overall 0.00509% 82/1,610,852 alleles · very rare exomes 77/1,458,572 · genomes 5/152,280 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00619%	16,153
South Asian	0.00554%	18,062
Admixed American	0.00336%	29,741
Remaining individualsnot grpmax-eligible	0.0016%	62,388
African / African-American	0.00133%	74,956

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: ANKRD27
Protein: p.Ala522Val
Coding: c.1565C>T
MANE Select: NM_032139
dbSNP: rs776736848
Type: single nucleotide variant
Location: chr19:32625938 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 5 PDB
Residue 522: the 'interaction with rab32' region; the 'interaction with rab38' region

Full ANKRD27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD27 p.Ala522Ser Uncertain significance ★ ⚠ same residue
ANKRD27 p.Ala199Ser Uncertain significance ★ ⚠ same type
ANKRD27 p.Ala2Val Uncertain significance ★ ⚠ same type
ANKRD27 p.Ala344Ser Uncertain significance ★ ⚠ same type
ANKRD27 p.Ala344Thr Uncertain significance ★ ⚠ same type
ANKRD27 p.Ala406Pro Uncertain significance ★ ⚠ same type
ANKRD27 p.Ala476Thr Uncertain significance ★ ⚠ same type
ANKRD27 p.Ala547Ser 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/ankrd27-p-ala522val (accessed [today's date]).

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