Is NCAPD2 p.Phe44Ser (c.131T>C) pathogenic?

NCAPD2 p.Phe44Ser (c.131T>C) is classified Uncertain significance in NCAPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely pathogenic (0.8191); Very rare (popmax 0.00533%, afr); Associated with Inborn genetic diseases.

What condition is associated with NCAPD2 p.Phe44Ser (c.131T>C)?

NCAPD2 p.Phe44Ser (c.131T>C) is associated with Inborn genetic diseases (ClinVar).

How common is NCAPD2 p.Phe44Ser (c.131T>C) in the general population?

NCAPD2 p.Phe44Ser (c.131T>C) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about NCAPD2 p.Phe44Ser (c.131T>C)?

AlphaMissense predicts likely pathogenic (score 0.8191) — an in-silico prediction, not a clinical call.

NCAPD2 p.Phe44Ser

c.131T>C · rs530151221 · VCV3180623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8191 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8191	likely pathogenic · top 10% in NCAPD2
REVEL	0.278	benign-leaning
SaProt	LLR -10.18	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 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 36 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	26.9	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 0.00533% African / African-American · 4/75,056 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00062% 10/1,614,032 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,764
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.000339%	294,982

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: NCAPD2
Protein: p.Phe44Ser
Coding: c.131T>C
MANE Select: NM_014865
dbSNP: rs530151221
Type: single nucleotide variant
Location: chr12:6509720 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.94
Residue 44: the 'interactions with smc2 and smc4' region

Full NCAPD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NCAPD2 c.2735-6C>T Uncertain significance ★★ same condition
NCAPD2 p.Ala43Gly Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Arg1397His Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Arg677His Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Asn598Ile Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Glu1178Lys Uncertain significance ★★ ⚠ same condition
NCAPD2 p.Glu883Lys Uncertain significance ★★ ⚠ same condition
NCAPD2 c.2482-6C>T 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/ncapd2-p-phe44ser (accessed [today's date]).

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