Is DNM1L p.Phe370Ser (c.1109T>C) pathogenic?

DNM1L p.Phe370Ser (c.1109T>C) is classified Pathogenic in DNM1L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1.

How common is DNM1L p.Phe370Ser (c.1109T>C) in the general population?

DNM1L p.Phe370Ser (c.1109T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNM1L p.Phe370Ser (c.1109T>C)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

DNM1L p.Phe370Ser

c.1109T>C · VCV3343933

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 4% in DNM1L
REVEL	0.935	strongly pathogenic-leaning
SaProt	LLR -15.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 10 kb · p 5.4e-15 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNM1L
Protein: p.Phe370Ser
Coding: c.1109T>C
MANE Select: NM_012062
Type: single nucleotide variant
Location: chr12:32731043 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 77.09 · 11 PDB
Residue 370: an α-helix; the 'middle domain' region

Full DNM1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNM1L p.Phe370Leu Likely pathogenic ★ same residue
DNM1L c.1596+2T>A Likely pathogenic ★★ same type
DNM1L c.1674+1G>A Pathogenic/Likely pathogenic ★★ same type
DNM1L p.Arg403Cys Pathogenic ★★ same type
DNM1L p.Arg530Ter Pathogenic/Likely pathogenic ★★ same type
DNM1L p.Asp146Asn Pathogenic/Likely pathogenic ★★ same type
DNM1L p.Cys431Tyr Pathogenic ★★ same type
DNM1L p.Gly362Ser 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/dnm1l-p-phe370ser (accessed [today's date]).

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