Is ANKRD27 p.Ser628Phe (c.1883C>T) pathogenic?

ANKRD27 p.Ser628Phe (c.1883C>T) is classified Uncertain significance in ANKRD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.1006); Ultra-rare (popmax 0.0903%, nfe).

How common is ANKRD27 p.Ser628Phe (c.1883C>T) in the general population?

ANKRD27 p.Ser628Phe (c.1883C>T) is ultra-rare (popmax 0.0903%, nfe) (gnomAD).

What do computational predictors say about ANKRD27 p.Ser628Phe (c.1883C>T)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

ANKRD27 p.Ser628Phe

c.1883C>T · rs141524480 · VCV3124489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0903%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.237	benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP -0.51, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 61 kb · p 0.24 · regional, not allelic
Overall
CADD	14.99	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 0.0903% European (non-Finnish) · 1,065/1,180,032 alleles

Filtering AF 0.0857% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0839%

Overall 0.0709% 1,145/1,613,972 alleles · ultra-rare exomes 1,051/1,461,846 · genomes 94/152,126 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0903%	1,108
Remaining individualsnot grpmax-eligible	0.0608%	1,644
African / African-American	0.0187%	5,351
Admixed American	0.0183%	5,455
South Asian	0.0176%	5,693
Middle Eastern	0.0164%	6,084

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.Ser628Phe
Coding: c.1883C>T
MANE Select: NM_032139
dbSNP: rs141524480
Type: single nucleotide variant
Location: chr19:32619498 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 5 PDB
Residue 628: the 'interaction with rab32' region; the 'disordered' region

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

Similar variants

ANKRD27 p.Ser628Pro 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-ser628phe (accessed [today's date]).

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