Is DMTF1 p.Ala548Thr (c.1642G>A) pathogenic?

DMTF1 p.Ala548Thr (c.1642G>A) is classified Uncertain significance in DMTF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.095); Very rare (popmax 0.00667%, afr).

How common is DMTF1 p.Ala548Thr (c.1642G>A) in the general population?

DMTF1 p.Ala548Thr (c.1642G>A) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about DMTF1 p.Ala548Thr (c.1642G>A)?

AlphaMissense predicts likely benign (score 0.095) — an in-silico prediction, not a clinical call.

DMTF1 p.Ala548Thr

c.1642G>A · VCV4241549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.095 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.095	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -4.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,032 bp · p 0.62 · regional, not allelic
Overall
CADD	22.6	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 0.00667% African / African-American · 5/74,950 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000496% 8/1,613,076 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,990
Remaining individualsnot grpmax-eligible	0.0048%	20,815

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.Ala548Thr
Coding: c.1642G>A
MANE Select: NM_001142327
Type: single nucleotide variant
Location: chr7:87193345 (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 548: the 'required for transcriptional activation' 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

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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-ala548thr (accessed [today's date]).

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