Is ANKH p.Ala435= (c.1305G>A) pathogenic?

ANKH p.Ala435= (c.1305G>A) is classified Likely benign in ANKH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-08). Very rare (popmax 0.005%, amr).

How common is ANKH p.Ala435= (c.1305G>A) in the general population?

ANKH p.Ala435= (c.1305G>A) is very rare (popmax 0.005%, amr) (gnomAD).

ANKH p.Ala435=

c.1305G>A · rs776360474 · VCV1487283

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -3.3
Overall
CADD	0.291	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,984 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00171% 25/1,461,332 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,995
European (non-Finnish)	0.00178%	56,187
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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: ANKH
Protein: p.Ala435=
Coding: c.1305G>A
MANE Select: NM_054027
dbSNP: rs776360474
Type: single nucleotide variant
Location: chr5:14712934 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.57

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

Similar variants

ANKH p.Ala435Val Conflicting classifications of pathogenicity ★ ⚠ same residue
ANKH c.1142-4A>G Pathogenic/Likely pathogenic ★★ same type
ANKH c.96+5G>A Uncertain significance ★★ same type
ANKH c.*3752G>A Uncertain significance ★★ same type
ANKH p.Ala136Thr Uncertain significance ★★ ⚠ same type
ANKH p.Ala201Thr Uncertain significance ★★ ⚠ same type
ANKH p.Ala448Thr Uncertain significance ★★ ⚠ same type
ANKH p.Arg453Gln 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/ankh-p-ala435 (accessed [today's date]).

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