Is ANKS6 p.Ser638= (c.1914G>A) pathogenic?

ANKS6 p.Ser638= (c.1914G>A) is classified Likely benign in ANKS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-29). Ultra-rare (popmax 0.0208%, eas); Associated with nephronophthisis 16.

What condition is associated with ANKS6 p.Ser638= (c.1914G>A)?

ANKS6 p.Ser638= (c.1914G>A) is associated with nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Ser638= (c.1914G>A) in the general population?

ANKS6 p.Ser638= (c.1914G>A) is ultra-rare (popmax 0.0208%, eas) (gnomAD).

How is Nephronophthisis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ANKS6 p.Ser638=

c.1914G>A · VCV4777351

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, eas)

Conditions

nephronophthisis 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.072	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.5	GERP -4.9
Overall
CADD	0.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0208% East Asian · 9/43,360 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00803%

Overall 0.0027% 39/1,443,004 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0208%	4,818
South Asian	0.00457%	21,905
Finnishnot grpmax-eligible	0.00313%	31,920
European (non-Finnish)	0.00196%	50,903
Admixed American	0.00174%	57,520

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: ANKS6
Protein: p.Ser638=
Coding: c.1914G>A
MANE Select: NM_173551
Type: single nucleotide variant
Location: chr9:98770954 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.60 · 1 PDB
Residue 638: the 'disordered' region

Full ANKS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

ANKS6 p.Ser638Leu Uncertain significance ★★ ⚠ same residue
ANKS6 c.1973-3C>G Pathogenic/Likely pathogenic ★★ same condition
ANKS6 p.Arg461Ter Pathogenic/Likely pathogenic ★★ same condition
ANKS6 c.907+6C>T Uncertain significance ★★ same condition
ANKS6 p.Ala215Thr Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala215Val Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala249Thr Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala261Thr 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/anks6-p-ser638 (accessed [today's date]).

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