Is DMAC2 p.Ser207Leu (c.620C>T) pathogenic?

DMAC2 p.Ser207Leu (c.620C>T) is classified Uncertain significance in DMAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-02). AlphaMissense: ambiguous (0.4095); Rare (popmax 0.585%, amr).

How common is DMAC2 p.Ser207Leu (c.620C>T) in the general population?

DMAC2 p.Ser207Leu (c.620C>T) is rare (popmax 0.585%, amr) (gnomAD).

What do computational predictors say about DMAC2 p.Ser207Leu (c.620C>T)?

AlphaMissense predicts ambiguous (score 0.4095) — an in-silico prediction, not a clinical call.

DMAC2 p.Ser207Leu

c.620C>T · VCV4660462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4095 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.585%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4095	ambiguous
REVEL	0.27	benign-leaning
SaProt	LLR -11.53	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.54, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,665 bp · p 0.25 · regional, not allelic
Overall
CADD	28.5	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 0.585% Admixed American · 351/60,012 alleles

Filtering AF 0.534% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.515%

Overall 0.0253% 408/1,613,960 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.585%	171
Remaining individualsnot grpmax-eligible	0.0384%	2,604
African / African-American	0.00533%	18,767
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.00229%	43,704
South Asian	0.0011%	91,086

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: DMAC2
Protein: p.Ser207Leu
Coding: c.620C>T
MANE Select: NM_018035
Type: single nucleotide variant
Location: chr19:41432385 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.56

Full DMAC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMAC2 p.Ser207= Likely benign ★ same residue
DMAC2 p.His23Arg Likely benign ★★ same type
DMAC2 p.Ala193Thr Uncertain significance ★ ⚠ same type
DMAC2 p.Ala237Thr Uncertain significance ★ ⚠ same type
DMAC2 p.Ala27Val Uncertain significance ★ ⚠ same type
DMAC2 p.Ala86Thr Uncertain significance ★ ⚠ same type
DMAC2 p.Arg107Ser Uncertain significance ★ ⚠ same type
DMAC2 p.Arg146Gly 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/dmac2-p-ser207leu (accessed [today's date]).

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