Is CIMAP1D p.Ser71Leu (c.212C>T) pathogenic?

CIMAP1D p.Ser71Leu (c.212C>T) is classified Uncertain significance in CIMAP1D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.3032); Very rare (popmax 0.00276%, afr).

How common is CIMAP1D p.Ser71Leu (c.212C>T) in the general population?

CIMAP1D p.Ser71Leu (c.212C>T) is very rare (popmax 0.00276%, afr) (gnomAD).

What do computational predictors say about CIMAP1D p.Ser71Leu (c.212C>T)?

AlphaMissense predicts likely benign (score 0.3032) — an in-silico prediction, not a clinical call.

CIMAP1D p.Ser71Leu

c.212C>T · rs1048680674 · VCV2493663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3032 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00276%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3032	likely benign
REVEL	0.635	indeterminate
SaProt	LLR -13.57	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 0.97, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.28 · regional, not allelic
Overall
CADD	24.4	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 0.00276% African / African-American · 2/72,450 alleles

Filtering AF 0.000985% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000812%

Overall 0.00136% 21/1,542,080 alleles · very rare exomes 19/1,389,940 · genomes 2/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00276%	36,225
East Asian	0.00251%	39,886
European (non-Finnish)	0.00158%	63,476

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: CIMAP1D
Protein: p.Ser71Leu
Coding: c.212C>T
MANE Select: NM_182577
dbSNP: rs1048680674
Type: single nucleotide variant
Location: chr19:472417 (GRCh38)
Structure: AlphaFold pLDDT 67.70

Full CIMAP1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1D p.Ala255Ser Uncertain significance ★ ⚠ same type
CIMAP1D p.Ala66Thr Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg101Cys Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg11Gln Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg11Trp Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg136His Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg138Trp Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg148Cys 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/cimap1d-p-ser71leu (accessed [today's date]).

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