Is ARPC1B p.Ser336Arg (c.1008C>A) pathogenic?

ARPC1B p.Ser336Arg (c.1008C>A) is classified Uncertain significance in ARPC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-17). AlphaMissense: likely benign (0.3323); Very rare (popmax 0.00746%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARPC1B p.Ser336Arg (c.1008C>A)?

ARPC1B p.Ser336Arg (c.1008C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC1B p.Ser336Arg (c.1008C>A) in the general population?

ARPC1B p.Ser336Arg (c.1008C>A) is very rare (popmax 0.00746%, nfe) (gnomAD).

What do computational predictors say about ARPC1B p.Ser336Arg (c.1008C>A)?

AlphaMissense predicts likely benign (score 0.3323) — an in-silico prediction, not a clinical call.

ARPC1B p.Ser336Arg

c.1008C>A · rs376347366 · VCV2461366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3323 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00746%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3323	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -9.72	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 -13	GERP -3.4
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	2.758	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00746% European (non-Finnish) · 88/1,180,028 alleles

Filtering AF 0.00615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00573%

Overall 0.00577% 93/1,613,076 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00746%	13,409
Remaining individualsnot grpmax-eligible	0.0032%	31,242
African / African-American	0.00267%	37,473
Finnishnot grpmax-eligible	0.00159%	63,002

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: ARPC1B
Protein: p.Ser336Arg
Coding: c.1008C>A
MANE Select: NM_005720
dbSNP: rs376347366
Type: single nucleotide variant
Location: chr7:99394047 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 336: a β-strand

Full ARPC1B 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

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ARPC1B p.Arg167Trp Uncertain significance ★★ ⚠ same condition
ARPC1B p.Arg216Cys Uncertain significance ★★ ⚠ same condition
ARPC1B p.Asn109Lys Uncertain significance ★★ ⚠ same condition
ARPC1B p.Asn327Ser Uncertain significance ★★ ⚠ same condition
ARPC1B p.Asp149Ala 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/arpc1b-p-ser336arg (accessed [today's date]).

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