Is NACA p.Pro1772Ser (c.5314C>T) pathogenic?

NACA p.Pro1772Ser (c.5314C>T) is classified Benign in NACA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-16). AlphaMissense: likely benign (0.0824); Rare (popmax 0.414%, nfe).

How common is NACA p.Pro1772Ser (c.5314C>T) in the general population?

NACA p.Pro1772Ser (c.5314C>T) is rare (popmax 0.414%, nfe) (gnomAD).

What do computational predictors say about NACA p.Pro1772Ser (c.5314C>T)?

AlphaMissense predicts likely benign (score 0.0824) — an in-silico prediction, not a clinical call.

NACA p.Pro1772Ser

c.5314C>T · rs183828032 · VCV713130

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0824 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.414%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0824	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 3,084 bp · p 0.49 · regional, not allelic
Overall
CADD	19.43	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 0.414% European (non-Finnish) · 4,881/1,179,890 alleles

Filtering AF 0.404% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.4%

Overall 0.37% 5,969/1,613,764 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.75%	57
Remaining individualsnot grpmax-eligible	0.528%	189
European (non-Finnish)grpmax	0.414%	242
Middle Eastern	0.198%	505
South Asian	0.119%	843
Admixed American	0.0883%	1,132
African / African-American	0.0666%	1,501
Finnishnot grpmax-eligible	0.0266%	3,753

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: NACA
Protein: p.Pro1772Ser
Coding: c.5314C>T
MANE Select: NM_001365896
dbSNP: rs183828032
Type: single nucleotide variant
Location: chr12:56716216 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 38.15 · 26 PDB
Residue 1772: the 'disordered' region

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

Similar variants

NACA p.Ala242= Benign ★★ same type
NACA p.Phe405Ser Benign ★★ same type
NACA p.Pro490Arg Benign ★★ same type
NACA p.Ala152Val Uncertain significance ★ ⚠ same type
NACA p.Ala1803Pro Uncertain significance ★ ⚠ same type
NACA p.Ala1833Val Uncertain significance ★ ⚠ same type
NACA p.Ala1868Val Uncertain significance ★ ⚠ same type
NACA p.Ala348Ser 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/naca-p-pro1772ser (accessed [today's date]).

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