Is ANKRD40 p.Pro130Ser (c.388C>T) pathogenic?

ANKRD40 p.Pro130Ser (c.388C>T) is classified Uncertain significance in ANKRD40 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.6059); Very rare (popmax 0.00338%, sas).

How common is ANKRD40 p.Pro130Ser (c.388C>T) in the general population?

ANKRD40 p.Pro130Ser (c.388C>T) is very rare (popmax 0.00338%, sas) (gnomAD).

What do computational predictors say about ANKRD40 p.Pro130Ser (c.388C>T)?

AlphaMissense predicts likely pathogenic (score 0.6059) — an in-silico prediction, not a clinical call.

ANKRD40 p.Pro130Ser

c.388C>T · VCV4640951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6059 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00338%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6059	likely pathogenic
REVEL	0.152	moderately benign-leaning
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.69, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 420 bp · p 0.88 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00338% South Asian · 3/88,752 alleles

Filtering AF 0.000898% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000449%

Overall 0.000208% 3/1,442,198 alleles · very rare

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: ANKRD40
Protein: p.Pro130Ser
Coding: c.388C>T
MANE Select: NM_052855
Type: single nucleotide variant
Location: chr17:50699789 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.38

Full ANKRD40 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD40 p.Ala242Thr Uncertain significance ★ ⚠ same type
ANKRD40 p.Ala350Thr Uncertain significance ★ ⚠ same type
ANKRD40 p.Arg13Lys Uncertain significance ★ ⚠ same type
ANKRD40 p.Arg177Gln Uncertain significance ★ ⚠ same type
ANKRD40 p.Arg217Cys Uncertain significance ★ ⚠ same type
ANKRD40 p.Arg347Thr Uncertain significance ★ ⚠ same type
ANKRD40 p.Asn122Lys Uncertain significance ★ ⚠ same type
ANKRD40 p.Asn145Ser 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/ankrd40-p-pro130ser (accessed [today's date]).

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