Is DRAM1 p.Ser231Tyr (c.692C>A) pathogenic?

DRAM1 p.Ser231Tyr (c.692C>A) is classified Uncertain significance in DRAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.1716); Very rare (popmax 8.53e-05%, nfe).

How common is DRAM1 p.Ser231Tyr (c.692C>A) in the general population?

DRAM1 p.Ser231Tyr (c.692C>A) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about DRAM1 p.Ser231Tyr (c.692C>A)?

AlphaMissense predicts likely benign (score 0.1716) — an in-silico prediction, not a clinical call.

DRAM1 p.Ser231Tyr

c.692C>A · VCV4244707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1716	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 39 bp · p 0.96 · regional, not allelic
Overall
CADD	25.1	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 8.53e-05% European (non-Finnish) · 1/1,172,750 alleles

Overall 0.000657% 1/152,152 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: DRAM1
Protein: p.Ser231Tyr
Coding: c.692C>A
MANE Select: NM_018370
Type: single nucleotide variant
Location: chr12:101921235 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.73

Full DRAM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRAM1 p.Ala169Thr Uncertain significance ★ ⚠ same type
DRAM1 p.Asn235Ile Uncertain significance ★ ⚠ same type
DRAM1 p.Asn235Ser Uncertain significance ★ ⚠ same type
DRAM1 p.Asn37Ile Uncertain significance ★ ⚠ same type
DRAM1 p.Glu187Ala Uncertain significance ★ ⚠ same type
DRAM1 p.Gly106Arg Uncertain significance ★ ⚠ same type
DRAM1 p.Gly54Asp Uncertain significance ★ ⚠ same type
DRAM1 p.Ile159Met 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/dram1-p-ser231tyr (accessed [today's date]).

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