Is ALS2 p.Ser370Phe (c.1109C>T) pathogenic?

ALS2 p.Ser370Phe (c.1109C>T) is classified Uncertain significance in ALS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). AlphaMissense: likely benign (0.0808); Absent from gnomAD v4.1.

How common is ALS2 p.Ser370Phe (c.1109C>T) in the general population?

ALS2 p.Ser370Phe (c.1109C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALS2 p.Ser370Phe (c.1109C>T)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

ALS2 p.Ser370Phe

c.1109C>T · rs1343472956 · VCV2662165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,946)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -8.85	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 4.3	GERP -0.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.0064 · regional, not allelic
Overall
CADD	11.96	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

No allele count reported in gnomAD v4.1 (AN 1,611,946). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALS2
Protein: p.Ser370Phe
Coding: c.1109C>T
MANE Select: NM_020919
dbSNP: rs1343472956
Type: single nucleotide variant
Location: chr2:201760885 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.69

Full ALS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALS2 c.1640+1G>A Pathogenic/Likely pathogenic ★★ same type
ALS2 c.2580+2T>C Pathogenic ★★ same type
ALS2 c.3703-2A>G Pathogenic/Likely pathogenic ★★ same type
ALS2 c.4626+1G>A Pathogenic/Likely pathogenic ★★ same type
ALS2 p.Ala573Glu Likely pathogenic ★★ same type
ALS2 p.Arg1139Ter Pathogenic/Likely pathogenic ★★ same type
ALS2 p.Arg1421Ter Pathogenic/Likely pathogenic ★★ same type
ALS2 p.Arg1461Ter Pathogenic ★★ 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/als2-p-ser370phe (accessed [today's date]).

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