Is ANP32D p.Arg14Ser (c.42G>T) pathogenic?

ANP32D p.Arg14Ser (c.42G>T) is classified Uncertain significance in ANP32D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.6315); Very rare (popmax 0.00223%, eas).

How common is ANP32D p.Arg14Ser (c.42G>T) in the general population?

ANP32D p.Arg14Ser (c.42G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ANP32D p.Arg14Ser (c.42G>T)?

AlphaMissense predicts likely pathogenic (score 0.6315) — an in-silico prediction, not a clinical call.

ANP32D p.Arg14Ser

c.42G>T · VCV3401462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6315 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6315	likely pathogenic
REVEL	0.188	benign-leaning
SaProt	LLR -9.82	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 5	phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 392 bp · p 0.16 · regional, not allelic
Overall
CADD	15.86	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 0.00223% East Asian · 1/44,884 alleles

Overall 6.84e-05% 1/1,461,880 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: ANP32D
Protein: p.Arg14Ser
Coding: c.42G>T
MANE Select: NM_012404
Type: single nucleotide variant
Location: chr12:48472706 (GRCh38)
Gene constraint: LOEUF 1.433 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 95.57

Full ANP32D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANP32D p.Arg14Gly Uncertain significance ★ ⚠ same residue
ANP32D p.Asn127Ile Uncertain significance ★ ⚠ same type
ANP32D p.Asn129Ser Uncertain significance ★ ⚠ same type
ANP32D p.Asn51Ile Uncertain significance ★ ⚠ same type
ANP32D p.Asp18Asn Uncertain significance ★ ⚠ same type
ANP32D p.Glu43Lys Uncertain significance ★ ⚠ same type
ANP32D p.Gly32Cys Uncertain significance ★ ⚠ same type
ANP32D p.His92Arg 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/anp32d-p-arg14ser (accessed [today's date]).

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