Is ANKRD16 p.Lys188Arg (c.563A>G) pathogenic?

ANKRD16 p.Lys188Arg (c.563A>G) is classified Uncertain significance in ANKRD16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-12). AlphaMissense: likely benign (0.0774); Very rare (popmax 0.00224%, sas).

How common is ANKRD16 p.Lys188Arg (c.563A>G) in the general population?

ANKRD16 p.Lys188Arg (c.563A>G) is very rare (popmax 0.00224%, sas) (gnomAD).

What do computational predictors say about ANKRD16 p.Lys188Arg (c.563A>G)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

ANKRD16 p.Lys188Arg

c.563A>G · VCV3867044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -5.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor loss, 27 bp away · masked 0 · deltas
Pangolin	Δ0.30	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.2	phastCons 0.74
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.64 · regional, not allelic
Overall
CADD	18.54	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 0.00224% South Asian · 2/89,352 alleles

Filtering AF 0.000372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000139%

Overall 0.000186% 3/1,608,686 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00224%	44,676
African / African-American	0.00134%	74,610

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: ANKRD16
Protein: p.Lys188Arg
Coding: c.563A>G
MANE Select: NM_019046
Type: single nucleotide variant
Location: chr10:5885738 (GRCh38)
Gene constraint: LOEUF 1.356 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.32

Full ANKRD16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD16 p.Ala208Thr Uncertain significance ★ ⚠ same type
ANKRD16 p.Ala21Ser Uncertain significance ★ ⚠ same type
ANKRD16 p.Ala234Ser Uncertain significance ★ ⚠ same type
ANKRD16 p.Ala240Thr Uncertain significance ★ ⚠ same type
ANKRD16 p.Ala359Thr Uncertain significance ★ ⚠ same type
ANKRD16 p.Ala36Thr Uncertain significance ★ ⚠ same type
ANKRD16 p.Arg146Gln Uncertain significance ★ ⚠ same type
ANKRD16 p.Arg20Leu 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/ankrd16-p-lys188arg (accessed [today's date]).

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