Is APCS p.Pro184Ser (c.550C>T) pathogenic?

APCS p.Pro184Ser (c.550C>T) is classified Likely benign in APCS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: likely benign (0.0628); Very rare (popmax 0.00267%, afr).

How common is APCS p.Pro184Ser (c.550C>T) in the general population?

APCS p.Pro184Ser (c.550C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about APCS p.Pro184Ser (c.550C>T)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

APCS p.Pro184Ser

c.550C>T · VCV3883460

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -4.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.5	GERP -4
Regional constraint	o/e 1.17	unconstrained · MANE · 783 bp · p 0.0074 · regional, not allelic
Overall
CADD	0.047	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 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000205% 3/1,461,834 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,467
European (non-Finnish)	8.47e-05%	1,179,960

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: APCS
Protein: p.Pro184Ser
Coding: c.550C>T
MANE Select: NM_001639
Type: single nucleotide variant
Location: chr1:159588586 (GRCh38)
Gene constraint: LOEUF 1.826 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 94.48 · 13 PDB
Residue 184: the pentraxin (ptx) domain; an α-helix

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

Similar variants

APCS p.Ala146Thr Uncertain significance ★ ⚠ same type
APCS p.Ala58Val Uncertain significance ★ ⚠ same type
APCS p.Arg64His Uncertain significance ★ ⚠ same type
APCS p.Arg86Gly Uncertain significance ★ ⚠ same type
APCS p.Asp203His Uncertain significance ★ ⚠ same type
APCS p.Gln74Glu Uncertain significance ★ ⚠ same type
APCS p.Glu118Lys Uncertain significance ★ same type
APCS p.Ile113Asn 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/apcs-p-pro184ser (accessed [today's date]).

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