Is ANKRD26 p.Ser680Phe (c.2039C>T) pathogenic?

ANKRD26 p.Ser680Phe (c.2039C>T) is classified Uncertain significance in ANKRD26 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-27). AlphaMissense: likely benign (0.1461); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with ANKRD26 p.Ser680Phe (c.2039C>T)?

ANKRD26 p.Ser680Phe (c.2039C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD26 p.Ser680Phe (c.2039C>T) in the general population?

ANKRD26 p.Ser680Phe (c.2039C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ANKRD26 p.Ser680Phe (c.2039C>T)?

AlphaMissense predicts likely benign (score 0.1461) — an in-silico prediction, not a clinical call.

ANKRD26 p.Ser680Phe

c.2039C>T · rs370286051 · VCV2499389

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1461 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1461	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.83	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 -2.2	GERP -1.1
Regional constraint	o/e 1.00	unconstrained · MANE · 65 kb · p 0.96 · regional, not allelic
Overall
CADD	11.77	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 0.00133% African / African-American · 1/74,918 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00093% 15/1,613,660 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,918
European (non-Finnish)	0.00119%	84,270

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: ANKRD26
Protein: p.Ser680Phe
Coding: c.2039C>T
MANE Select: NM_014915
dbSNP: rs370286051
Type: single nucleotide variant
Location: chr10:27043548 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.91
Residue 680: the 'disordered' region

Full ANKRD26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANKRD26 p.Ala1014Ser Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1015Val Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala120Thr Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1215Thr Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1284Ser Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1416Val Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1503Ser Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1505Thr Uncertain significance ★★ ⚠ same condition

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/ankrd26-p-ser680phe (accessed [today's date]).

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