Is ANP32D p.Phe41Ser (c.122T>C) pathogenic?

ANP32D p.Phe41Ser (c.122T>C) is classified Uncertain significance in ANP32D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely pathogenic (0.827); Very rare (popmax 0.00133%, afr).

How common is ANP32D p.Phe41Ser (c.122T>C) in the general population?

ANP32D p.Phe41Ser (c.122T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ANP32D p.Phe41Ser (c.122T>C)?

AlphaMissense predicts likely pathogenic (score 0.827) — an in-silico prediction, not a clinical call.

ANP32D p.Phe41Ser

c.122T>C · VCV3875438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.827	likely pathogenic · top 4% in ANP32D
REVEL	0.23	benign-leaning
SaProt	LLR -14.37	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 392 bp · p 0.16 · regional, not allelic
Overall
CADD	17.01	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 0.00133% African / African-American · 1/74,928 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,928
European (non-Finnish)	0.000254%	393,345

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.Phe41Ser
Coding: c.122T>C
MANE Select: NM_012404
Type: single nucleotide variant
Location: chr12:48472786 (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 type
ANP32D p.Arg14Ser Uncertain significance ★ ⚠ same type
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

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-phe41ser (accessed [today's date]).

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