Is CFLAR p.Asn382Ser (c.1145A>G) pathogenic?

CFLAR p.Asn382Ser (c.1145A>G) is classified Likely benign in CFLAR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely benign (0.0819); Ultra-rare (popmax 0.0439%, sas).

How common is CFLAR p.Asn382Ser (c.1145A>G) in the general population?

CFLAR p.Asn382Ser (c.1145A>G) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

What do computational predictors say about CFLAR p.Asn382Ser (c.1145A>G)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

CFLAR p.Asn382Ser

c.1145A>G · rs751374408 · VCV2382687

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.001	strongly benign-leaning
SaProt	LLR -5.11	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 -0.87	GERP -3.7
Regional constraint	o/e 0.79	unconstrained · MANE · 28 kb · p 5.8e-05 · regional, not allelic
Overall
CADD	0.034	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 0.0439% South Asian · 40/91,070 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00322% 52/1,614,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0048%	20,830
Admixed American	0.00333%	30,003
European (non-Finnish)	0.000593%	168,575

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: CFLAR
Protein: p.Asn382Ser
Coding: c.1145A>G
MANE Select: NM_003879
dbSNP: rs751374408
Type: single nucleotide variant
Location: chr2:201160783 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.84 · 17 PDB
Residue 382: the 'interaction with casp8 subunits p18 and p10' region; the 'interaction with casp8' region; the 'not proteolytically processed and involved in apoptosis inhibition' region; the 'interaction with traf1 and traf2' region; the 'interaction with casp3' region

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

Similar variants

CFLAR p.Leu203Ile Benign ★★ same type
CFLAR p.Val375= Benign ★★ same type
CFLAR p.Ala178Thr Uncertain significance ★ ⚠ same type
CFLAR p.Ala349Ser Uncertain significance ★ ⚠ same type
CFLAR p.Arg303Ter Uncertain significance ★ same type
CFLAR p.Arg315Gln Uncertain significance ★ ⚠ same type
CFLAR p.Arg397Pro Uncertain significance ★ ⚠ same type
CFLAR p.Asn199Ser 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/cflar-p-asn382ser (accessed [today's date]).

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