Is ANKRD16 p.Arg9Ser (c.25C>A) pathogenic?

ANKRD16 p.Arg9Ser (c.25C>A) is classified Uncertain significance in ANKRD16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: likely benign (0.2109); Very rare (popmax 0.00805%, nfe).

How common is ANKRD16 p.Arg9Ser (c.25C>A) in the general population?

ANKRD16 p.Arg9Ser (c.25C>A) is very rare (popmax 0.00805%, nfe) (gnomAD).

What do computational predictors say about ANKRD16 p.Arg9Ser (c.25C>A)?

AlphaMissense predicts likely benign (score 0.2109) — an in-silico prediction, not a clinical call.

ANKRD16 p.Arg9Ser

c.25C>A · VCV3866986

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00805%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2109	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.88, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.64 · regional, not allelic
Overall
CADD	18.07	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 0.00805% European (non-Finnish) · 81/1,006,148 alleles

Filtering AF 0.0066% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00604%

Overall 0.00666% 84/1,260,740 alleles · very rare exomes 75/1,108,986 · genomes 9/151,754 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00805%	12,422
Remaining individualsnot grpmax-eligible	0.00428%	23,354
African / African-American	0.00155%	64,406

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.Arg9Ser
Coding: c.25C>A
MANE Select: NM_019046
Type: single nucleotide variant
Location: chr10:5889330 (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-arg9ser (accessed [today's date]).

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