Is ASAP2 p.Ser855Arg (c.2565C>G) pathogenic?

ASAP2 p.Ser855Arg (c.2565C>G) is classified Uncertain significance in ASAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: ambiguous (0.3959); Very rare (popmax 0.00323%, nfe).

How common is ASAP2 p.Ser855Arg (c.2565C>G) in the general population?

ASAP2 p.Ser855Arg (c.2565C>G) is very rare (popmax 0.00323%, nfe) (gnomAD).

What do computational predictors say about ASAP2 p.Ser855Arg (c.2565C>G)?

AlphaMissense predicts ambiguous (score 0.3959) — an in-silico prediction, not a clinical call.

ASAP2 p.Ser855Arg

c.2565C>G · rs778807638 · VCV2372564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00323%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3959	ambiguous
REVEL	0.134	moderately benign-leaning
SaProt	LLR -8.51	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.4	GERP -3.7
Regional constraint	o/e 0.93	unconstrained · MANE · 44 kb · p 0.076 · regional, not allelic
Overall
CADD	4.161	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 0.00323% European (non-Finnish) · 38/1,175,918 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00243% 39/1,603,524 alleles · very rare exomes 38/1,451,546 · genomes 1/151,978 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00323%	30,945
Finnishnot grpmax-eligible	0.00162%	61,582

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: ASAP2
Protein: p.Ser855Arg
Coding: c.2565C>G
MANE Select: NM_003887
dbSNP: rs778807638
Type: single nucleotide variant
Location: chr2:9393528 (GRCh38)
Gene constraint: LOEUF 0.465 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.71
Residue 855: the 'disordered' region

Full ASAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAP2 p.Ser855Cys Uncertain significance ★ ⚠ same residue
ASAP2 p.Ala592= Benign ★★ same type
ASAP2 p.Asp434= Benign ★★ same type
ASAP2 p.Asp45= Benign ★★ same type
ASAP2 p.Pro868Leu Benign ★★ same type
ASAP2 c.687-1G>T Uncertain significance ★ same type
ASAP2 p.Ala1005Thr Uncertain significance ★ ⚠ same type
ASAP2 p.Ala276Thr 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/asap2-p-ser855arg (accessed [today's date]).

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