Is AKNA p.Pro970Ser (c.2908C>T) pathogenic?

AKNA p.Pro970Ser (c.2908C>T) is classified Uncertain significance in AKNA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely benign (0.0789); Very rare (popmax 0.00133%, afr).

How common is AKNA p.Pro970Ser (c.2908C>T) in the general population?

AKNA p.Pro970Ser (c.2908C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about AKNA p.Pro970Ser (c.2908C>T)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

AKNA p.Pro970Ser

c.2908C>T · VCV3850216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.34	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 -0.1	GERP -3.9
Regional constraint	o/e 0.96	unconstrained · MANE · 44 kb · p 0.12 · regional, not allelic
Overall
CADD	5.863	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 · 1/74,912 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,058 alleles · very rare exomes 4/1,461,884 · genomes 3/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,912
European (non-Finnish)	0.000508%	196,673

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: AKNA
Protein: p.Pro970Ser
Coding: c.2908C>T
MANE Select: NM_001317950
Type: single nucleotide variant
Location: chr9:114356075 (GRCh38)
Gene constraint: LOEUF 0.631 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.46

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

Similar variants

AKNA p.Ala1053Val Uncertain significance ★★ ⚠ same type
AKNA p.Arg351Gln Uncertain significance ★★ ⚠ same type
AKNA p.Ala1006= Benign ★★ same type
AKNA p.Ala1051= Benign ★★ same type
AKNA p.Arg506Cys Benign ★★ same type
AKNA p.Leu111= Benign ★★ same type
AKNA p.Leu544Val Benign ★★ same type
AKNA p.Val962Met Benign ★★ 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/akna-p-pro970ser (accessed [today's date]).

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