Is ANKRD27 p.Arg756Pro (c.2267G>C) pathogenic?

ANKRD27 p.Arg756Pro (c.2267G>C) is classified Uncertain significance in ANKRD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-21). AlphaMissense: likely pathogenic (0.8635); Very rare (popmax 0.00167%, amr).

How common is ANKRD27 p.Arg756Pro (c.2267G>C) in the general population?

ANKRD27 p.Arg756Pro (c.2267G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ANKRD27 p.Arg756Pro (c.2267G>C)?

AlphaMissense predicts likely pathogenic (score 0.8635) — an in-silico prediction, not a clinical call.

ANKRD27 p.Arg756Pro

c.2267G>C · rs761307804 · VCV2259513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8635	likely pathogenic
REVEL	0.424	indeterminate
SaProt	LLR -15.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 61 kb · p 0.24 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/59,866 alleles

Overall 6.2e-05% 1/1,612,880 alleles · very rare exomes 1/1,460,562 · genomes 0/152,318 · joint denominator

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.Arg756Pro
Coding: c.2267G>C
MANE Select: NM_032139
dbSNP: rs761307804
Type: single nucleotide variant
Location: chr19:32607741 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 5 PDB

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

Similar variants

ANKRD27 p.Arg756Gln 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.Ala522Ser 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-arg756pro (accessed [today's date]).

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