Is ANKRD16 p.Leu209Ser (c.626T>C) pathogenic?

ANKRD16 p.Leu209Ser (c.626T>C) is classified Uncertain significance in ANKRD16 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely pathogenic (0.7003); Very rare (popmax 0.00133%, afr).

How common is ANKRD16 p.Leu209Ser (c.626T>C) in the general population?

ANKRD16 p.Leu209Ser (c.626T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ANKRD16 p.Leu209Ser (c.626T>C)?

AlphaMissense predicts likely pathogenic (score 0.7003) — an in-silico prediction, not a clinical call.

ANKRD16 p.Leu209Ser

c.626T>C · rs1446041686 · VCV2308370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7003 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7003	likely pathogenic
REVEL	0.646	pathogenic-leaning
SaProt	LLR -15.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.64 · regional, not allelic
Overall
CADD	24.7	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 0.00133% African / African-American · 1/74,954 alleles

Overall 0.000657% 1/152,268 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: ANKRD16
Protein: p.Leu209Ser
Coding: c.626T>C
MANE Select: NM_019046
dbSNP: rs1446041686
Type: single nucleotide variant
Location: chr10:5884030 (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-leu209ser (accessed [today's date]).

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