Is DMTF1 p.Phe185Ser (c.554T>C) pathogenic?

DMTF1 p.Phe185Ser (c.554T>C) is classified Uncertain significance in DMTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). AlphaMissense: likely pathogenic (0.9994); Very rare (popmax 8.61e-05%, nfe).

How common is DMTF1 p.Phe185Ser (c.554T>C) in the general population?

DMTF1 p.Phe185Ser (c.554T>C) is very rare (popmax 8.61e-05%, nfe) (gnomAD).

What do computational predictors say about DMTF1 p.Phe185Ser (c.554T>C)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

DMTF1 p.Phe185Ser

c.554T>C · VCV3272440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.61e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 5% in DMTF1
REVEL	0.621	indeterminate
SaProt	LLR -12.39	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 15 kb · p 1.1e-16 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.61e-05% European (non-Finnish) · 1/1,161,860 alleles

Overall 7.12e-05% 1/1,404,748 alleles · very rare

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: DMTF1
Protein: p.Phe185Ser
Coding: c.554T>C
MANE Select: NM_001142327
Type: single nucleotide variant
Location: chr7:87179579 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.72 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 1 PDB
Residue 185: the 'interaction with ccnd2' region; the 'required for dna-binding' region; the 'interaction with ccnd1, ccnd2 and ccnd3' region

Full DMTF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMP1 p.Gly135Ter Pathogenic/Likely pathogenic ★★ same type
DMP1 p.Met1Val Pathogenic/Likely pathogenic ★★ same type
DMP1 c.*159T>A Uncertain significance ★★ same type
DMP1 c.*77T>C Uncertain significance ★★ same type
DMP1 p.Arg173Trp Uncertain significance ★★ ⚠ same type
DMP1 p.Arg302Ile Uncertain significance ★★ ⚠ same type
DMP1 p.Arg310Lys Uncertain significance ★★ ⚠ same type
DMP1 p.Asn233Lys 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/dmtf1-p-phe185ser (accessed [today's date]).

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