Is ANKZF1 p.Pro570Ser (c.1708C>T) pathogenic?

ANKZF1 p.Pro570Ser (c.1708C>T) is classified Benign in ANKZF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.2864); Low-frequency (popmax 3.76%, afr).

How common is ANKZF1 p.Pro570Ser (c.1708C>T) in the general population?

ANKZF1 p.Pro570Ser (c.1708C>T) is low-frequency (popmax 3.76%, afr) (gnomAD).

What do computational predictors say about ANKZF1 p.Pro570Ser (c.1708C>T)?

AlphaMissense predicts likely benign (score 0.2864) — an in-silico prediction, not a clinical call.

ANKZF1 p.Pro570Ser

c.1708C>T · rs77280560 · VCV775821

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2864 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.76%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2864	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -7.96	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 3.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 6,184 bp · p 0.4 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.76% African / African-American · 2,819/74,956 alleles

Filtering AF 3.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.6%

Overall 0.204% 3,294/1,613,896 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.76%	27
Middle Eastern	0.514%	195
Remaining individualsnot grpmax-eligible	0.278%	359
Admixed American	0.277%	361
South Asian	0.0154%	6,505
European (non-Finnish)	0.00763%	13,111

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: ANKZF1
Protein: p.Pro570Ser
Coding: c.1708C>T
MANE Select: NM_018089
dbSNP: rs77280560
Type: single nucleotide variant
Location: chr2:219235490 (GRCh38)
Gene constraint: LOEUF 1.125 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.09

Full ANKZF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKZF1 p.Pro570Leu Uncertain significance ★★ ⚠ same residue
ANKZF1 p.Ala251Asp Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala269Thr Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala287Val Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala327Thr Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala391Val Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala486Thr Uncertain significance ★★ ⚠ same type
ANKZF1 p.Ala529Val 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/ankzf1-p-pro570ser (accessed [today's date]).

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